[ CAS No. 32281-97-3 ] {[proInfo.proName]}

Name: 32281-97-3|7-Bromo-3,4-dihydronaphthalen-1(2H)-one|98%
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Quality Control of [ 32281-97-3 ]

COA NMR CNMR HPLC LC-MS

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Product Citations

Synthesis and Evaluation of Bislawsone Derivatives as Possible Electrolytes for Redox Flow Batteries

Jennifer Doan Tran ; Harvard University,2024.

Abstract: As climate change continues to be a global issue due to its negative environmental impact, various countries have made great efforts to integrate more renewable energy into the power-grid. Using renewable energy can lower dependency on fossil fuels but, there are issues that limit switching from consuming fossil fuels to renewable energy. In the case of solar or wind technology, the energy harnessed is not consistent throughout the day. By pairing renewable energy with redox flow batteries (RFBs), this can address the issue of inconsistent energy. Through RFBs, excess energy generated by renewable energy can be stored by electrochemical bonds. The focus of this research is to synthesize a water-soluble bislawsone to use as a redox active material for RFBs using 7-bromo-3,4-dihydro-2H-naphthalen-1-one. 2,2’-bis(3-hydroxy-7-methoxy-N,N,N-trimethylethanaminium chloride-1,4-naphthoquinone) was made but was not purified. The crude product was used in cyclic voltammetry (CV) testing. As a baseline, 5 mM of 7,7’-dibromo-2,2’-bis(3-hydroxy-1,4-naphthoquinone) was added to 1M KOH and the CV was measured. The potential was measured at -0.637 V. The electrolytic solution consisted of 5 mM of redox active material with 1M KCl in water adjusted to pH 7. There was no measurement. The second electrolytic solution consisted of 5 mM of redox active material with 1M KCl in 1M KOH. The potential was measured at -0.628 V. Solubility decreased by adding supporting salts and at pH 7. This suggests that adding a water-soluble group on bislawsone influences solubility and solubility affects voltage potential.

Purchased from AmBeed: 32281-97-3

Product Details of [ 32281-97-3 ]

CAS No. :	32281-97-3	MDL No. :	MFCD02179287
Formula :	C₁₀H₉BrO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YGVDCGFUUUJCDF-UHFFFAOYSA-N
M.W :	225.08	Pubchem ID :	252731
Synonyms :	NSC 74917;7-Bromotetralone	Chemical Name :	7-Bromo-3,4-dihydronaphthalen-1(2H)-one

Calculated chemistry of [ 32281-97-3 ] Expand+

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.3
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	52.0
TPSA :	17.07 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.75 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.23
Log Po/w (XLOGP3) :	2.71
Log Po/w (WLOGP) :	2.97
Log Po/w (MLOGP) :	2.71
Log Po/w (SILICOS-IT) :	3.68
Consensus Log Po/w :	2.86

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.31
Solubility :	0.11 mg/ml ; 0.000487 mol/l
Class :	Soluble
Log S (Ali) :	-2.72
Solubility :	0.427 mg/ml ; 0.0019 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.25
Solubility :	0.0125 mg/ml ; 0.0000557 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.89

Safety of [ 32281-97-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P273	UN#:	N/A
Hazard Statements:	H302-H412	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 32281-97-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 32281-97-3 ]
Downstream synthetic route of [ 32281-97-3 ]

[ 32281-97-3 ] Synthesis Path-Upstream 1~7

1
[ 32281-97-3 ]
[ 51934-39-5 ]

Reference： [1] Journal of Organic Chemistry, 1962, vol. 27, p. 76 - 78

2
[ 32281-97-3 ]
[ 1680-51-9 ]

Reference： [1] Journal of Organic Chemistry, 1984, vol. 49, # 22, p. 4226 - 4237

3
[ 32281-97-3 ]
[ 6134-56-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	at 20 - 50℃; for 4 h;	(2) Synthesis of 6-bromo-1,2,3,4-tetrahydronaphthalene To 7.50 g of 7-bromo-3,4-dihydronaphthalen-1(2H)-one in trifluoroacetic acid (60 ml), 15.5 g of triethylsilane was added dropwise over 30 minutes at room temperature (the temperature of the reaction solution exothermically elevated from 27° C. to 50° C.). After the dropwise addition, the reaction solution was allowed to react at room temperature for 2 hours and then on a water bath at 50° C. for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was poured into 400 ml of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate (200 ml1, 100 ml1). The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane) to obtain 6.63 g of the desired product (yield 94percent). Morphology: pale yellow oil

Reference： [1] Patent: US2012/209005, 2012, A1, . Location in patent: Page/Page column 30
[2] Organic Letters, 2018, vol. 20, # 7, p. 2042 - 2045

4
[ 529-34-0 ]
[ 32281-97-3 ]
[ 68449-30-9 ]

Yield	Reaction Conditions	Operation in experiment
51%	at 80℃;	Example 1; Preparation of 7-Bromo-l-tetralone; 7-bromo-1-tetralone was prepared according to the procedure described in Cornelius, L. A. M.; Combs, D. W. Synthetic Communications 1994,24, 2777-2788. The above isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-bromo-1-tetralone (11.59 g, 51percent) and 7-bromo-1-tetralone (9.45 g, 42percent).
42%	at 75 - 80℃; for 0.55 h;	A 500 mL three-necked flask fitted with an addition funnel, reflux condenser and thermometer was charged with aluminum chloride (33.34 g, 250 mmol) and heated to 75-80 °C. 1- Tetralone (14.6 g, 13.3 ML, 100 mmol) was added dropwise over 10 min. The resulting brown slurry was stirred for 3 min before dropwise addition of bromine (19.21 g, 6.15 ml, 120 mmol) over 15 min. The mixture was stirred for 5 min and then poured into a mixture of ice (300 g) and 12N HC1 (40 mL). The mixture was stirred until the aluminum chloride was dissolved and then diluted with water (200 mL). The mixture was extracted with diethyl ether (3 X 300 mL) and the combined organics were washed with water (2 X 300 mL), dried (sodium sulfate), filtered and evaporated in vacuo to give a dark brown mixture of 5-and 7- BROMO-1-TETRALONE. The isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-BROMO-1-TETRALONE (11.59 g, 51percent) and 7- BROMO-1-TETRALONE (9.45 g, 42percent).
42%	Stage #1: at 75 - 80℃; for 0.216667 h; Stage #2: for 0.333333 h;	A 500 mL three-necked flask fitted with an addition funnel, reflux condenser and thermometer was charged with aluminum chloride (33.-34 g, 250 mmol) and heated to 75-80 °C. 1- Tetralone (14.6 g, 13.3 mL, 100 mmol) was added dropwise over 10 MIN. THE resulting brown slurry was stirred for 3 min before dropwise addition of bromine (19.21 g, 6.15 ml, 120 mmol) over 15 min. The mixture was stirred for 5 min and then poured into a mixture of ice (300 g) and 12N HC1 (40 mL). The mixture was stirred until the aluminum chloride was dissolved and then diluted with water (200 mL). The mixture was extracted with diethyl ether (3 X 300 mL) and the combined organics were washed with water (2 X 300 mL), dried (sodium sulfate), filtered and evaporated in vacuo to give a dark brown mixture of 5-and 7- BROMO-1-TETRALONE. The isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-BROMO-1-TETRALONE (11.59 g, 51percent) and 7- BROMO-1-TETRALONE (9.45 g, 42percent). [Note 1. Procedure: Cornelius, L. A. M.; Combs, D. W. Synthetic Communications 1994,24, 2777-2788].

Reference： [1] Patent: WO2005/95326, 2005, A2, . Location in patent: Page/Page column 110-111
[2] Patent: WO2004/94384, 2004, A2, . Location in patent: Page 63-64
[3] Patent: WO2004/94413, 2004, A1, . Location in patent: Page 63-64
[4] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 1, p. 29 - 35
[5] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 16, p. 4405 - 4409
[6] Synthetic Communications, 1994, vol. 24, # 19, p. 2777 - 2788
[7] Gazzetta Chimica Italiana, 1988, vol. 118, # 5, p. 369 - 374
[8] Patent: US5753655, 1998, A,
[9] Patent: US2004/6229, 2004, A1, . Location in patent: Page/Page column 13-14
[10] Organic and Biomolecular Chemistry, 2017, vol. 15, # 6, p. 1381 - 1392
[11] Patent: US2003/225281, 2003, A1, . Location in patent: Page 12

5
[ 529-34-0 ]
[ 32281-97-3 ]
[ 68449-30-9 ]

Yield	Reaction Conditions	Operation in experiment
28.3%	Stage #1: Under N₂ Stage #2: at 80℃; for 0.0833333 h;	Anhydrous AlCl3 (66.67 g, 0.50 mol, 99.99percent) under N2 was stirred vigorously as 1-tetralone (29.83 g, 0.20 mol) was added dropwise over 7 min. The evolved HCl gas was scrubbed through 5 N NaOH. The resulting mixture was a dark brown oil that exothermed to 75° C. When the temperature had cooled to 50° C., Br2 was added dropwise over 15 min. The mixture, which had cooled further to 40° C., was heated to 80° C. for 5 min, then poured into a mixture of ice (600 g) and 12 N HCl (80 mL). All the ice melted, leaving a cool dark mixture which was diluted with H2O (200 mL) and extracted with CH2Cl2 (200 mL, 100 mL). The combined extracts were dried with MgSO4 and concentrated in vacuo (30-60° C.) to a dark brown oil (45.6 g; theory=45.02 g).[0085] Chromatography over silica gel 60 with 8:1 heptane:THF did not prove effective, but two passes through the Biotage radially pressured silica gel cartridges using 9:1 heptane:MTBE as eluent produced acceptably pure fractions. [0086] 5-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as an orange oil (12.27 g, 28.3percent). HPLC showed an apparent wide divergence in absorbances at 230 nm for the two regioisomers, and was therefore not reliable for a potency check. TLC on silica gel (4:1 heptane:MTBE) confirmed modest contamination with 7-bromo-3,4-dihydro-1(2H)-naphthalenone. [0087] 7-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as a yellowish-white solid (15.48 g, 35.8percent); mp 69.5-75° C. (lit 74-75° C.). 1H NMR (CDCl3) corresponded to the literature description, plus a trace of heptane and an undefined by-product. TLC showed it to be cleaner than 5-bromo-3,4-dihydro-1(2H)-naphthalenone. [0088] A third fraction of orange oil (9.06 g, 20.9percent) was isolated. TLC showed it to be a nearly 1:1 ratio of 5-bromo-3,4-dihydro-1(2H)-naphthalenone, and 7-bromo-3,4-dihydro-1(2H)-naphthalenone.

Reference： [1] Patent: US2003/232833, 2003, A1, . Location in patent: Page 12

6
[ 32281-97-3 ]
[ 91270-69-8 ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: With tetra-N-butylammonium tribromide In methanol; dichloromethane at 20℃; for 16 h; Stage #2: With lithium carbonate; lithium bromide In N,N-dimethyl-formamide at 140℃; for 1.5 h;	Step D: A solution of tetrabutylammonium tribromide (11.8 g, 24.4 mmol) in dichloromethane (80 ml) was added dropwise to a solution of the product from Step C (5.0 g, 22.2 mmol) in dichloromethane (20 ml) and methanol (20 ml) at room temperature over 1 hour. At completion of the addition, the mixture was stirred at room temperature for 15 hours and was then concentrated. The residue was taken into dichloromethane and was washed with saturated sodium bicarbonate three times. The organic layer was concentrated and the residue was dissolved in dimethylformamide (100 ml). Lithium carbonate (5.3 g, 71.1 mmol) and lithium bromide (4.1 g, 46.6 mmol) were added and the resulting mixture was stirred at 140° C. for 1.5 hours. After cooling to room temperature, the solids were filtered and rinsed with ethyl acetate. The filtrate was washed with water four times and dried over sodium sulfate to give 7-bromonaphthalen-1-ol (2.7 g, 56percent): ¹H NMR (300 MHz, CDCl₃) δ 8.41 (d, J=1.8 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.57 (dd, J=8.7, 1.8 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.28-7.35 (m, 1H), 6.62 (d, J=7.2 Hz, 1H), 5.80 (br s, 1H).

Reference： [1] Patent: US2006/52378, 2006, A1, . Location in patent: Page/Page column 113
[2] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 12, p. 1199 - 1203

7
[ 67-56-1 ]
[ 201230-82-2 ]
[ 32281-97-3 ]
[ 116047-26-8 ]

Reference： [1] Patent: WO2015/176267, 2015, A1, . Location in patent: Page/Page column 116

[ 32281-97-3 ] Synthesis Path-Downstream 1~109

1
[ 32281-97-3 ]
[ 2243-56-3 ]
[ 122447-23-8 ]

Reference： [1]Journal of Organic Chemistry,1951,vol. 16,p. 309,312

2
[ 32281-97-3 ]
[ 2243-58-5 ]
9-bromo-12,13-dihydro-7<i>H</i>-dibenzo[<i>a,g</i>]carbazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1951,vol. 16,p. 309,312

3
[ 32281-97-3 ]
[ 59-88-1 ]
[ 21064-46-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	With hydrogenchloride In ethanol; water at 90℃; for 12h;	1.a Synthesis of intermediate A-2-1 Phenylhydrazine hydrochloride (70.0 g,484.1 mmoles) and 7-bromo-3,4-dihydro-2H-naphthalen-1-one (108.9 g, 484.1 mmoles) were placed in a round bottom flask and subsequently dissolved in ethanol (1200 ml) .60 ml of hydrochloric acid was slowly added dropwise thereto at room temperature,And the resulting mixture was stirred at 90 ° C for 12 hours. When the reaction is complete,Remove the solvent from it under reduced pressure,And an extract was obtained therefrom by using an excess of EA.After removing the organic solvent under reduced pressure,The extract was stirred in a small amount of methanol and then filtered to obtain 95.2 g of Intermediate A-2-1 (66%).
66%	With hydrogenchloride In ethanol; water at 90℃; for 12h;	1.a Synthesis intermediate A-2-1 Phenylhydrazine hydrochloride (70.0 g, 484.1 mmol) and 7-bromo-3,4-dihydro-2H-naphthalen-1-one (108.9 g, 484.1 mmol) were placed in a round bottom flask and then dissolved In ethanol (1200 ml). 60 ml of hydrochloric acid was slowly added dropwise thereto at room temperature,And the obtained mixture was stirred at 90 ° C for 12 hours. When the reaction is complete,The solvent was removed therefrom under reduced pressure, and an extract was obtained therefrom using an excess of ethyl acetate (EA). After removing the organic solvent under reduced pressure,The extract was stirred in a small amount of methanol and then filtered,This gave 95.2 g of intermediate A-2-1 (66%).
66%	With hydrogenchloride In ethanol; water at 90℃; for 12h;	1.a a) Synthesis of Intermediate A-2-1 Phenylhydrazinehydrochloride (70.0 g, 484.1 mmol) and 7-bromo-3,4-dihydro-2H-naphthalen-1-one (108.9 g, 484.1 mmol) were put in a round-bottomed flask and then, dissolved in ethanol (1200 ml). Subsequently, 60 mL of hydrochloric acid was slowly added thereto in a dropwise fashion at room temperature and then, stirred at 90° C. for 12 hours. When a reaction was complete, the solvent was removed therefrom under a reduced pressure, and an excessive amount of EA was used for extraction. After removing the EA under a reduced pressure, the residue was stirred in a small amount of methanol and then, filtered to obtain 95.2 g (66%) of Intermediate A-2-1.

	With ethanol; sodium acetate Erhitzen des Reaktionsprodukts mit Chlorwasserstoff enthaltender Essigsaeure;
	With acetic acid In ethanol Reflux;

Reference： [1]Current Patent Assignee: SAMSUNG ELECTRONICS CO.,LTD.; SAMSUNG SDI CO.,LTD. - TW2019/43698, 2019, A Location in patent: Paragraph 0116-0119
[2]Current Patent Assignee: SAMSUNG ELECTRONICS CO.,LTD.; SAMSUNG SDI CO.,LTD. - TW2019/43699, 2019, A Location in patent: Paragraph 0178-0180
[3]Current Patent Assignee: SAMSUNG SDI CO.,LTD.; SAMSUNG ELECTRONICS CO.,LTD. - US2021/70706, 2021, A1 Location in patent: Paragraph 0163-0165
[4]Buu-Hoi et al. [Journal of Organic Chemistry, 1951, vol. 16, p. 309,312]
[5]Current Patent Assignee: LG CHEM CO.,LTD. - KR2016/29721, 2016, A Location in patent: Paragraph 0401-0402

4
[ 6628-03-1 ]
[ 32281-97-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	With Fe-Al-MCM-41 molecular sieve In toluene at 60℃; for 18h; Green chemistry;	6 Example 6 Add 10mmol of the compound of formula (I) and 20mL of dichloromethane to the reactor successively, add 20mmol of oxalyl chloride dropwise to the reactor under an ice bath, and then raise the temperature to reflux for 2 hours after the completion of the drop. After the reaction is completed, it is evaporated to dryness in vacuo to obtain (II) The crude 4-phenylbutyryl chloride compound was dissolved in 20 mL of toluene, and Fe-Al-MCM-41 molecular sieve was added to start the reaction. Stir at 60°C for 18 hours. After the reaction is completed, return to room temperature and filter with suction. The molecular sieve catalyst was washed with toluene and recovered, the filtrate was combined and evaporated to dryness in vacuo. The residue was purified by silica gel column chromatography to obtain the benzocyclohexanone compound of formula (III) with a yield of 84.0%.
	With carbon disulfide; aluminium trichloride at 0℃;

Reference： [1]Current Patent Assignee: OCEAN UNIVERSITY OF CHINA - CN112094182, 2020, A Location in patent: Paragraph 0041-0043
[2]Fieser; Seligman [Journal of the American Chemical Society, 1938, vol. 60, p. 170,174]

5
[ 35656-89-4 ]
[ 32281-97-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With PPA at 90℃; for 0.25h;
95%	With PPA at 90℃; for 2h;
95%	With phosphorus pentoxide In toluene at 110℃; for 2h;	1 Example 1 The effect of the ratio of the amount of the different condensing agent on the yield of the product.The use of phosphorus pentoxide as a dehydrating agent, the use of toluene as the solvent, the fixed reaction temperature was 110 , the reaction time was 2h,Exploring the effect of the ratio of 4 - (4 - bromophenyl) butanoic acid and phosphorus pentoxide on the product yield, the results are shown in Table 1. ;_ The ratio of the amount of 4- (4 - bromophenyl) butyric acid and phosphorus pentoxide fixed in 1: 3 was determined by using toluene as solvent and the reaction time was 2h. The effect of different reaction temperature on the yield of product was explored. The results are shown in Table 2. ;_ Fixing the ratio of the amount of substance of 4- (4 - bromophenyl) butyric acid: phosphorus pentoxide to 1: 3, using toluene as solvent and the reaction temperature of 110 , the effects of different time on product yield were explored,The results are shown in Table 3.

84%	With polyphosphoric acid at 90℃; for 1h;	3.2.1 (1) Synthesis of 7-bromo-3,4-dihydronaphthalen-1(2H)-one 10.1 g of 4-(4-bromophenyl)butanoic acid was added in portions to 100 g of polyphosphoric acid heated to 90° C. with stirring. After 1 hour of reaction, the reaction mixture was poured into 300 ml of ice-cold water with stirring, and the precipitated yellow solid was collected by filtration, washed with water and dissolved in a solvent mixture of 300 ml of ether and 100 ml of water. The ether layer was collected, and the aqueous layer was extracted with 75 ml of ether, and the extract was combined with the ether layer, washed with 30 ml of saturated aqueous sodium carbonate twice and with 50 ml of water twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was recrystallized from hexane to obtain 7.9 g of the desired product (yield 84%). Morphology: light brown crystals
83%	With PPA at 90℃; for 0.333333h;
75%	With PPA at 80℃; for 1h;
58%	With trifluorormethanesulfonic acid at 20℃; for 5h; Schlenk technique; Inert atmosphere;
55%	With PPA at 90℃; for 0.166667h;	63.C Step C: The product from Step B (97 g, 397 mmol) was added to polyphosphoric acid (580 g) and the resulting mixture was stirred at 90° C. for 10 minutes. After cooling to 0° C., 6 M NaOH (2 l) was added and the mixture was extracted with methyl tert-butyl ether. The organic extracts were dried over magnesium sulfate to give 7-bromo-3,4-dihydronaphthalen-1-one (49 g, 55%) after chromatography (6:1 to 4:1 heptane/ethyl acetate) and recrystallization from cyclohexane: 1H NMR (300 MHz, DMSO-d6) δ 7.91 (d, J=2.1 Hz, 1H), 7.71 (dd, J=8.1, 2.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 2.90 (t, J=6.0 Hz, 2H), 2.61 (t, J=6.3 Hz, 2H), 1.99-2.07 (m, 2H).
	With PPA
	With aluminium trichloride In carbon disulfide Yield given;
5 g	With phosphorus pentaoxide; phosphoric acid at 165℃; for 10h;
	With methanesulfonic acid; phosphorus pentoxide at 20℃; for 12h;
	Multi-step reaction with 2 steps 1: thionyl chloride 2: AlCl₃; carbon disulfide / 0 °C
	With polyphosphoric acid at 90℃;
	Multi-step reaction with 2 steps 1: oxalyl dichloride / dichloromethane / 2 h / 0 °C / Reflux; Green chemistry 2: Fe-Al-MCM-41 molecular sieve / toluene / 18 h / 60 °C / Green chemistry

Reference： [1]Mallory, Frank B.; Luzik, Eddie D.; Mallory, Clelia W.; Carroll, Patrick J. [Journal of Organic Chemistry, 1992, vol. 57, # 1, p. 366 - 370]
[2]Sommer; Rheingold; Goshe; Bosnich [Journal of the American Chemical Society, 2001, vol. 123, # 17, p. 3940 - 3952]
[3]Current Patent Assignee: BAI YIN LONG MING CHEMICAL TECH - CN107141202, 2017, A Location in patent: Paragraph 0011-0013; 0014-0016; 0017-0019
[4]Current Patent Assignee: NISSAN CHEMICAL CORPORATION - US2012/209005, 2012, A1 Location in patent: Page/Page column 30
[5]Chackal-Catoen, Sarah; Miao, Yi; Wilson, W. David; Wenzler, Tanja; Brun, Reto; Boykin, David W. [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 22, p. 7434 - 7445]
[6]Heller, Douglas P.; Goldberg, Daniel R.; Wu, Hongqiao; Wulff, William D. [Canadian Journal of Chemistry, 2006, vol. 84, # 10, p. 1487 - 1503]
[7]Saravanan, Perumal; Anbarasan, Pazhamalai [Advanced Synthesis and Catalysis, 2018, vol. 360, # 15, p. 2894 - 2899]
[8]Current Patent Assignee: CURIA INC - US2006/52378, 2006, A1 Location in patent: Page/Page column 113
[9]Buckle; Cantello; Smith; Spicer [Journal of Medicinal Chemistry, 1977, vol. 20, # 8, p. 1059 - 1064] Bonnier,J.-M.; Rinaudo,J. [Bulletin de la Societe Chimique de France, 1971, p. 2092 - 2094] Newman,M.S.; Seshadri,S. [Journal of Organic Chemistry, 1962, vol. 27, p. 76 - 78] Griffin,R.W. et al. [Journal of Organic Chemistry, 1964, vol. 29, # 8, p. 2109 - 2116]
[10]Gruber, Rene; Cagniant, Denise; Cagniant, Paul [Bulletin de la Societe Chimique de France, 1983, vol. 2, # 3-4, p. 96 - 104]
[11]Janczewski, Marian; Jablonska-Pikus, Teresa [Polish Journal of Chemistry, 1980, vol. 54, # 6, p. 1155 - 1169]
[12]Vercouillie, Johnny; Abarbri, Mohamed; Parrain, Jean-Luc; Duchene, Alain; Thibonnet, Jerome [Synthetic Communications, 2004, vol. 34, # 20, p. 3751 - 3762]
[13]Fieser; Seligman [Journal of the American Chemical Society, 1938, vol. 60, p. 170,174]
[14]Chen, Hui; Zhao, Sihan; Cheng, Shaobing; Dai, Xingjie; Xu, Xiaoying; Yuan, Weicheng; Zhang, Xiaomei [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 5, p. 1672 - 1683]
[15]Current Patent Assignee: OCEAN UNIVERSITY OF CHINA - CN112094182, 2020, A

6
[ 32281-97-3 ]
[ 75693-15-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium tetrahydridoborate In methanol; dichloromethane at 20 - 23℃; for 1h;
100%	With methanol; sodium tetrahydridoborate In dichloromethane at 20℃; for 1h;	156.1 Step 1: 7-bromo-1,2,3,4-tetrahydronaphthalen-1-ol (156a) To a cold solution of 7-bromo-1,2,3,4-tetrahydronaphthalen-1-one (225 mg, 1 mmol) in DCM (1.5 ml) and methanol (3 ml) was added dropwise NaBH4 (95 mg, 2.5 mmol). The reaction mixture was stirred 1 hour at room temperature and quenched with water. The aqueous layer was extracted with DCM. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give compound (156a) (229 mg, 1 mmol, 100%) 1H NMR (400 MHz, CDCl3) δ 1.73-1.87 (m, 2H), 1.92-2.02 (m, 2H), 2.61-2.68 (m, 1H), 2.72-2.79 (m, 1H), 4.73 (m, 1H), 6.96 (d, J = 8.2 Hz, 1H), 7.29 (dd, J = 8.2/2.1 Hz, 1H), 7.58 (d, J = 2.1 Hz, 1H). MS m/z ([M-H2O+H]+) 209-211.
92%	With methanol; sodium tetrahydridoborate at 20℃;

89%	With methanol; sodium tetrahydridoborate at 25℃; for 1h;	66 7-Bromo-1 ,2,3,4-tetrahydronaphthalen-1 -ol To a solution of 7-bromo-3,4-dihydronaphthalen-1 (2H)-one (2000 mg, 8.89 mmol) in methanol (20 mL) at 25 00 NaB H4 (672 mg, 1 7.77 mmol) was added. After the reaction mixture was stirred for 2 h, 1 N HCI solution was added to quench the reaction and extracted with ethyl acetate (3 x 50 mL). The combined organic layer was washed with brine (50 mL), dried overMgSO4, and concentrated to obtain the title compound 7-bromo-1 ,2,3,4-tetrahydronaphthalen-1 - ol (1800 mg, 7.93 mmol, 89% yield) as an oil. 1H NMR (400MHz, ODd3) 5 = 7.58 (d, J= 1.2 Hz, 1 H), 7.3-7.26 (m, 1 H), 6.97 (d, J= 7.2 Hz 1 H), 4.72 (s, 1 H), 2.74 (m, 2H), 2.04-1.87 (m, 5H).
89%	With methanol; sodium tetrahydridoborate at 25℃; for 2h;	66 7-Bromo-1,2,3,4-tetrahydronaphthalen- To a solution of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (2000 mg, 8.89 mmol) in methanol (20 mL) at 25 °C, NaBH4 (672 mg, 17.77 mmol) was added. After the reaction mixture was stirred for 2 h, 1N HCl solution was added to quench the reaction and extracted with ethyl acetate (3 x 50 mL). The combined organic layer was washed with brine (50 mL), dried over MgSO4, and concentrated to obtain the title compound 7-bromo-1,2,3,4-tetrahydronaphthalen-1- ol (1800 mg, 7.93 mmol, 89 % yield) as an oil. 1H NMR (400MHz, CDCl3) δ = 7.58 (d, J = 1.2 Hz, 1H), 7.3 - 7.26 (m, 1H), 6.97 (d, J = 7.2 Hz 1H), 4.72 (s, 1H), 2.74 (m, 2H), 2.04-1.87 (m, 5H).
87%	With sodium tetrahydridoborate In tetrahydrofuran; ethanol
65%	With sodium tetrahydridoborate In methanol; dichloromethane at 0 - 20℃;
59%	With sodium tetrahydridoborate In ethanol	2. General preparation of racemic alcohols (2a-7a) and standard racemic acetates (1b-7b) General procedure: 2-Tetralone, and 7-substituted-1-tetralones were reduced to racemic alcohols (2a-7a) by NaBH4 in dry ethanol with a similar method reported previously.4 1-Tetralone (1a) was purchased from Aldrich Chemical Co. Racemic alcohols (1a-7a) were acetylated to racemic acetates (1b-7b) by acetic anhydride with pyridine in dichloromethane.
	With sodium tetrahydridoborate In ethanol for 2h; Ambient temperature;
	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With sodium tetrahydridoborate In ethanol at 0 - 20℃; for 0.5h; Stage #2: With lithium hydroxide monohydrate In toluene	A.A Step A:; 7-Bromo-1,2,3,4-tetrahydronaphth-1-ol To 9.5 g of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (42 mmol), prepared according to the method described in Synth. Comm. 1994, 2777, dissolved in 100 ml of ethanol, there are added, at 0° C. and in two portions, 0.8 g of sodium borohydride (21 mmol). The reaction mixture is then allowed to come back up to ambient temperature over 30 minutes, and then the ethanol is evaporated off. The residue is taken up in 100 ml of toluene and 100 ml of water. After separation, the aqueous phase is extracted with 50 ml of toluene. The toluene phases are combined, washed with a saturated aqueous solution of sodium chloride and are then evaporated to yield 7-bromo-1,2,3,4-tetrahydronaphth-1-ol in the form of an oil.
	With sodium tetrahydridoborate In methanol; dichloromethane at 0℃; for 1.5h;	5.a a) 7-Bromo-1 ,2,3,4-tetrahydro-naphthalen-1 -ol; To a solution of 7-bromo-3,4-dihydro-2H-naphthalen-1-one (CASNo. 32281-97-3, 3.5 g, 0.015 mol) in methanol (7 ml.) and dichloromethane (10 mL) at 0 0C is added sodium borohydride (1.47 g, 0.038 mol) in one portion. The cooling bath is removed and after 1.5 hours, the mixture is poured into water and the volatile organics are removed in vacuo. Extraction with dichloromethane, drying over sodium sulfate, filtering through a cotton plug and concentration in vacuo affords 7-bromo-1 ,2,3,4-tetrahydro-naphthalen-1-ol. 1H NMR (400 MHz, CDCI3) δ ppm 1.72 (d, J=6.3 Hz, 1 H), 1.74 - 1.90 (m, 2 H), 1.92 - 2.07 (m, 2 H), 2.62 - 2.71 (m, 1 H), 2.73 - 2.82 (m, 1 H), 4.73 - 4.77 (m, 1 H), 6.98 (d, J=8.2 Hz1 1 H), 7.31 (dd, J=8.2, 2.1 Hz, 1 H), 7.61 (d, J=2.1 Hz, 1 H).
	With methanol; sodium tetrahydridoborate In dichloromethane at 20℃; Cooling;	9.1 Step 1 Sodium borohydride (0.53 g, 14 mmol) was added in small portions to a pre-cooled solution of 7-bromo-1-tetralone in DCM (15 mL) and MeOH (30 mL). After the addition, the mixture was stirred at RT for 90 min and then quenched with water (60 mL). The organic layer was separated. The aqueous layer was extracted with Et2O (4×30 mL). The combined extracts were washed sequentially with 1.0 N aq. HCl (3×20 mL), sat. aq. Na2CO3 (3×20 mL), and brine (2×20 mL), and then dried over anhydrous Na2SO4. Removal of the solvent using reduced pressure yielded 9A as an oil (3.02 g).
	With sodium tetrahydridoborate In methanol at 20℃; for 1.5h;
	With sodium tetrahydridoborate
	With sodium tetrahydridoborate In tetrahydrofuran; methanol at 0 - 20℃; for 3h;

Reference： [1]Saito, Masahiko; Kayama, Yasutaka; Watanabe, Tamaki; Fukushima, Hisashi; Hara, Takeshi; et al. [Journal of Medicinal Chemistry, 1980, vol. 23, # 12, p. 1364 - 1372]
[2]Current Patent Assignee: PHARMA OMNIUM INTERNATIONAL P O I - EP2913330, 2015, A1 Location in patent: Paragraph 0569
[3]Mikhael, Myriam; Adler, Sophia A.; Wengryniuk, Sarah E. [Organic Letters, 2019, vol. 21, # 15, p. 5889 - 5893]
[4]Current Patent Assignee: OTSUKA HOLDINGS CO LTD; GLAXOSMITHKLINE PLC - WO2016/203401, 2016, A1 Location in patent: Page/Page column 211
[5]Current Patent Assignee: GLAXOSMITHKLINE PLC; OTSUKA HOLDINGS CO LTD - WO2018/104766, 2018, A1 Location in patent: Page/Page column 212
[6]Adamczyk, Maciej; Watt, David S.; Netzel, Daniel A. [Journal of Organic Chemistry, 1984, vol. 49, # 22, p. 4226 - 4237]
[7]Walters, Jennifer C.; Tierno, Anthony F.; Dubin, Aimee H.; Wengryniuk, Sarah E. [European Journal of Organic Chemistry, 2018, vol. 2018, # 12, p. 1460 - 1464]
[8]Hoang, Hai Nam; Matsuda, Tomoko; Suzuki, Yuichi; Tamura, Mayumi; Taniguchi, Kosuke [Tetrahedron Letters, 2022, vol. 99]
[9]Chini, Marco; Crotti, Paolo; Minutolo, Filippo; Martinelli, Adriano; Micali, Eugenio [Gazzetta Chimica Italiana, 1994, vol. 124, # 1, p. 27 - 34]
[10]Current Patent Assignee: SERVIER MONDE - US2006/229318, 2006, A1 Location in patent: Page/Page column 6-7
[11]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2008/76336, 2008, A2 Location in patent: Page/Page column 72-73
[12]Current Patent Assignee: LIGAND PHARMACEUTICALS INC; MERCK & CO INC - US2010/197562, 2010, A1 Location in patent: Page/Page column 37
[13]Trenner, Johanna; Depken, Christian; Weber, Thomas; Breder, Alexander [Angewandte Chemie - International Edition, 2013, vol. 52, # 34, p. 8952 - 8956][Angew. Chem., 2013, vol. 125, # 34, p. 9121 - 9125,5]
[14]Li, Lijun; Su, Cunxiang; Liu, Xiaoqin; Tian, Hua; Shi, Yian [Organic Letters, 2014, vol. 16, # 14, p. 3728 - 3731]
[15]Guo, Rui; Sang, Jiale; Xiao, Haijing; Li, Junxia; Zhang, Guozhu [Chinese Journal of Chemistry, 2022, vol. 40, # 11, p. 1337 - 1345]

7
[ 32281-97-3 ]
[ 877263-91-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydroxylamine hydrochloride; sodium acetate In ethanol for 2h; Heating / reflux;	A; 1052.A Commercially available 7-bromo-3,4-dihydro-1(2H)-naphthalenone (3.0 g), hydroxylamine hydrochloride (2.8 g) and sodium acetate (3.4 g) in ethanol (60 mL) were refluxed for 2 h, evaporated, suspended in ethyl acetate and washed with water and brine. After evaporation the title compound (3.27 g; quantitative) was obtained as an off-white solid. [MH]+=240/242.
95%	With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 80℃; for 0.75h;	12.1 Step 1 : To a solution of sodium acetate (7.47 g, 91 mmol) in Water (13.33 mL) was added hydroxylamine hydrochloride (6.33 g, 91 mmol), then Ethanol (40 mL) and 7- bromo-3,4-dihydronaphthalen-l(2H)-one (10.25 g, 45.5 mmol). The white slurry was heated at 80°C for 45 minutes. Reaction was removed from heat, stirred for 10 minutes, then poured over ice and stirred until all ice melted. Filtered resulting solid, rinsed with water and dried to give a white solid (10.58 g, 95%). 1H NMR (DMSO-d6) δ: 11.29 (s, 1H), 7.94 (d, J = 2.0 Hz, 1H), 7.42 (dd, J = 8.2, 2.1 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 2.66 (dt, J = 16.9, 6.3 Hz, 4H), 1.74 (quin, J = 6.4 Hz, 2H); MS (m/z) 240/242 (M+H+), bromine splitting pattern.
93%	With hydroxylamine hydrochloride; sodium acetate In ethanol at 80℃; for 2h;	Intermediate 201A 7-bromo-N-hydroxy-3,4-dihydronaphthalen-1(2H)-imine A mixture of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (40.0 g, 178 mmol), hydroxylamine hydrochloride (37.0 g, 533 mmol) and sodium acetate (45.2 g, 551 mmol) in 200 ml ethanol was stirred at 80°C for 2 h. After cooling to room temperature, 100 ml water was added, and the eth- anol was removed under reduced pressure. The solid was collected by filtration, washed with water and dried in the oven to give 41.0 g (93% of theory, 97% purity) of the title compound. LC/MS [Method 6]: Rt = 1.11 min; MS (ESIpos): m/z = 240 [M+H]+. 1H-NMR (400 MHz, CDCIs): d [ppm] = 8.06 (d, 1H), 7.37 (dd, 1H), 7.03 (d, 1H), 2.79 (t, 2H), 2.71 (t, 2H), 1.89-1.83 (m, 2H).

86%	With hydroxylamine hydrochloride; sodium acetate In methanol at 20℃; for 3.5h;	59.B Step B: Sodium acetate (12.4 g, 150 mmol) was added to a solution of hydroxylamine hydrochloride (10.6 g, 150 mmol) in methanol (230 ml) at room temperature and the resulting mixture was stirred at room temperature for 30 minutes. The product from Step A (30.9 g, 140 mmol) was added portionwise over 1 hour and the mixture was stirred at room temperature for 2.5 hours. Water (300 ml) was added, the mixture became clear at first and then solids started to precipitate. The suspension was stirred at room temperature for 1 hour and then was filtered. The resulting solids were azeotroped with ethyl acetate three times to give the desired oxime (28.3 g, 86%): 1H NMR (300 MHz, DMSO-d6) δ 7.94 (d, J=0.9 Hz, 1H), 7.40 (dd, J=8.4, 1.2 Hz, 1H), 7.15 (d, J=8.1 Hz, 1H), 2.61-2.68 (m, 4H), 1.68-1.78 (m, 2H).
86%	With pyridine; hydroxylamine hydrochloride at 20℃; for 3h;	4.1.3. General produce for the preparation of 2,3,4,5-tetrahydro-1Hbenzo[b]azepine by reductive ring expansion General procedure: Hydroxylamine hydrochloride (2 equiv) was added to a stirredsolution of 3,4-dihydronaphthalen-1(2H)-one in pyridine (1 equiv).After the mixture was stirred for 3 h at room temperature, pyridinewas removed under reduced pressure. Then the products wereisolated following recrystallizations from aqueous ethanol. Moreover, the mixture could be extracted by EtOAc and purified bycolumn chromatography (PE/EA 5/1) to yield corresponding 3,4-dihydronaphthalen-1(2H)-one oxime.DIBALH (1Min n-hexane, 6 equiv)was added to a stirred solutionof 3,4-dihydronaphthalen-1(2H)-one oxime inCH2Cl2 drop by drop at0 C. Then the mixture was transferred to room temperature andstirred for another 2 h. The reaction was quenched carefully byaddition of NaF (12 equiv) and water at 0 C. The aluminum saltprecipitated out as colloid. Then the mixture was stirred at roomtemperature for another 2 h, and aluminumsaltwas filtered as sandlikesolid. The filtrate was dried over Na2SO4 and concentrated invacuo. The crude product was purified by column chromatography(Al2O3, PE/EA 5:1) to give 2,3,4,5-tetrahydro-1H-benzo[b]azepine.Then the designed compounds were obtained as methodsabove.
	With sodium hydroxide; hydroxylamine hydrochloride In ethanol; water Heating;
	With hydroxylamine hydrochloride; sodium acetate In methanol at 60℃; for 2h;
	With hydroxylamine hydrochloride; sodium acetate In ethanol; water
	With hydroxylamine hydrochloride; potassium acetate In ethanol at 80℃; for 2h; Inert atmosphere;	12 7-Bromo-3,4-dihydronaphthalen-1(2H)-one oxime A solution of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (10.0 g, 44.43 mmol), NH2OH.HCl (3.4 g, 48.87 mmol) and KOAc (6.54 g, 66.64 mmol) in EtOH (200 mL) stirred at 80°C for 2 h under N2. The solution was concentrated, and the solid residue was filtered, washed with water, and dried to afford the crude title compound (14.3 g), which was used without further purification.

Reference： [1]Current Patent Assignee: AMGEN INC - US2006/173183, 2006, A1 Location in patent: Page/Page column 106-107
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/125444, 2014, A1 Location in patent: Page/Page column 70
[3]Current Patent Assignee: BAYER AG - WO2019/219517, 2019, A1 Location in patent: Page/Page column 176
[4]Current Patent Assignee: CURIA INC - US2006/52378, 2006, A1 Location in patent: Page/Page column 111
[5]Guo, Zheng; Zhang, Zixue; Zhang, Yi; Wang, Guan; Huang, Ziyi; Zhang, Qinwei; Li, Jianqi [European Journal of Medicinal Chemistry, 2021, vol. 218]
[6]Mallory, Frank B.; Luzik, Eddie D.; Mallory, Clelia W.; Carroll, Patrick J. [Journal of Organic Chemistry, 1992, vol. 57, # 1, p. 366 - 370]
[7]Zhang, Minmin; Yu, Shuowen; Hu, Fangzhi; Liao, Yijun; Liao, Lihua; Xu, Xiaoying; Yuan, Weicheng; Zhang, Xiaomei [Chemical Communications, 2016, vol. 52, # 56, p. 8757 - 8760]
[8]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2018/26371, 2018, A1 Location in patent: Paragraph 0161
[9]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2021/87093, 2021, A1 Location in patent: Paragraph 00196-00197

8
[ 32281-97-3 ]
[ 111773-13-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With toluene-4-sulfonic acid In toluene Dean Stark;

Reference： [1]Zimmerman, Steven C.; VanZyl, Craig M. [Journal of the American Chemical Society, 1987, vol. 109, # 25, p. 7894 - 7896]

9
[ 32281-97-3 ]
[ 107-21-1 ]
[ 111773-13-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With toluene-4-sulfonic acid In benzene at 105℃; for 48h;
99%	With toluene-4-sulfonic acid In benzene for 24h; Heating / reflux; Dean-Stark apparatus;	34.1 A solution of 7-bromotetralone (5.0 g, 22.21 mmol) in benzene (100 mL) containing ethylene glycol (5.0 mL, 88.8 mmol) and p-toluenesulfonic acid monohydrate (420 mg, 2.22 mmol) was heated at reflux in a Dean-Stark apparatus for 24 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the resulting residue partitioned between ethyl acetate and water. The phases were separated, and the organic phase was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield the desired dioxolane (5.97 g, 99%) as a golden oil :'H NMR (300 MHz, CDC13) 8 7.57 (d, J = 2.0 Hz, 1 H), 7.32 (dd, J = 8.2, 2.0 Hz, 1 H), 6.96 (d, J = 8.2 Hz, 1 H), 4.23-4. 07 (m, 4H), 2.73-2. 72 (m, 2H), 2.04-1. 94 (m, 4H).
92%	With toluene-4-sulfonic acid In toluene for 12h; Heating;

83%

With VO(OTf)2*5H₂O In benzene for 12h; Reflux;

Reference： [1]Sommer; Rheingold; Goshe; Bosnich [Journal of the American Chemical Society, 2001, vol. 123, # 17, p. 3940 - 3952]
[2]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY - WO2005/87714, 2005, A2 Location in patent: Page/Page column 182-183
[3]Zimmerman, Steven C.; VanZyl, Craig M.; Hamilton, Gregory S. [Journal of the American Chemical Society, 1989, vol. 111, # 4, p. 1373 - 1381]
[4]Chen, Wen-Ching; Lee, Yi-Wei; Chen, Chien-Tien [Organic Letters, 2010, vol. 12, # 7, p. 1472 - 1475]

10
[ 529-34-0 ]
[ 32281-97-3 ]
[ 68449-30-9 ]

Yield	Reaction Conditions	Operation in experiment
42%; 51%	With bromine;aluminum (III) chloride; at 80℃;	Example 1; Preparation of 7-Bromo-l-tetralone; 7-bromo-1-tetralone was prepared according to the procedure described in Cornelius, L. A. M.; Combs, D. W. Synthetic Communications 1994,24, 2777-2788. The above isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-bromo-1-tetralone (11.59 g, 51%) and 7-bromo-1-tetralone (9.45 g, 42%).
42%; 51%	With aluminum (III) chloride; bromine; at 75 - 80℃; for 0.55h;	A 500 mL three-necked flask fitted with an addition funnel, reflux condenser and thermometer was charged with aluminum chloride (33.34 g, 250 mmol) and heated to 75-80 C. 1- Tetralone (14.6 g, 13.3 ML, 100 mmol) was added dropwise over 10 min. The resulting brown slurry was stirred for 3 min before dropwise addition of bromine (19.21 g, 6.15 ml, 120 mmol) over 15 min. The mixture was stirred for 5 min and then poured into a mixture of ice (300 g) and 12N HC1 (40 mL). The mixture was stirred until the aluminum chloride was dissolved and then diluted with water (200 mL). The mixture was extracted with diethyl ether (3 X 300 mL) and the combined organics were washed with water (2 X 300 mL), dried (sodium sulfate), filtered and evaporated in vacuo to give a dark brown mixture of 5-and 7- BROMO-1-TETRALONE. The isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-BROMO-1-TETRALONE (11.59 g, 51%) and 7- BROMO-1-TETRALONE (9.45 g, 42%).
42%; 51%		A 500 mL three-necked flask fitted with an addition funnel, reflux condenser and thermometer was charged with aluminum chloride (33.-34 g, 250 mmol) and heated to 75-80 C. 1- Tetralone (14.6 g, 13.3 mL, 100 mmol) was added dropwise over 10 MIN. THE resulting brown slurry was stirred for 3 min before dropwise addition of bromine (19.21 g, 6.15 ml, 120 mmol) over 15 min. The mixture was stirred for 5 min and then poured into a mixture of ice (300 g) and 12N HC1 (40 mL). The mixture was stirred until the aluminum chloride was dissolved and then diluted with water (200 mL). The mixture was extracted with diethyl ether (3 X 300 mL) and the combined organics were washed with water (2 X 300 mL), dried (sodium sulfate), filtered and evaporated in vacuo to give a dark brown mixture of 5-and 7- BROMO-1-TETRALONE. The isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-BROMO-1-TETRALONE (11.59 g, 51%) and 7- BROMO-1-TETRALONE (9.45 g, 42%). [Note 1. Procedure: Cornelius, L. A. M.; Combs, D. W. Synthetic Communications 1994,24, 2777-2788].

	With hydrogenchloride; bromine;aluminium trichloride; In tetrahydrofuran; hexane;	7-Bromo-1-tetralone (IXa) and 5-bromo-1-tetralone (IXb) STR10 1-Tetralone (VII) (7.3 g, 0.05 mol) was added dropwise to anhydrous aluminum chloride (16.6 g, 0.125 mol) with vigorous stirring over 3 minutes. Bromine (3.71 mL, 0.06 mol) was added to the resulting slurry over 10 minutes. The mixture was heated to 80 C. for 5 minutes after the addition of bromine was complete and the still molten mixture was poured into 150 g of crushed ice containing 20 ml of 12N HCl. Following the same work up as for example 1, 10.85 g of a brown oil was obtained. The oil was chromatographed on a silica gel column (45*10 cm) using hexane:THF (8:1). The separated isomers were each recrystallized from hexane to give 4.2 g of 7-bromo-1-tetralone (IXa) and 4.5 g of 5-bromo-1-tetralone (IXb).
		Preparation 1 [0086] Preparation of 1-Bromo-5-methoxy-naphthalene. [CHEMMOL-00020] [0087] Preparation of 5-Bromo-3,4-dihydro-1(2H)-naphthalenone and 7-bromo-3,4-dihydro-1(2H)-naphthalenone. [0088] Anhydrous AlCl3 (66.67 g, 0.50 mol, 99.99%) under N2 was stirred vigorously as 1-tetralone (29.83 g, 0.20 mol) was added dropwise over 7 min. The evolved HCl gas was scrubbed through 5 N NaOH. The resulting mixture was a dark brown oil that exothermed to 75 C. When the temperature had cooled to 50 C., Br2 was added dropwise over 15 min. The mixture, which had cooled further to 40 C., was heated to 80 C. for 5 min, then poured into a mixture of ice (600 g) and 12 N HCl (80 mL). All the ice melted, leaving a cool dark mixture which was diluted with H2O (200 mL) and extracted with CH2Cl2 (200 mL, 100 mL). The combined extracts were dried with MgSO4 and concentrated in vacuo (30-60 C.) to a dark brown oil (45.6 g; theory=45.02 g). [0089] Chromatography over silica gel 60 with 8:1 heptane:THF did not prove effective, but two passes through the Biotage radially pressured silica gel cartridges using 9:1 heptane:MTBE as eluent produced acceptably pure fractions. [0090] 5-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as an orange oil (12.27 g, 28.3%). HPLC showed an apparent wide divergence in absorbances at 230 nm for the two regioisomers, and was therefore not reliable for a potency check. TLC on silica gel (4:1 heptane:MTBE) confirmed modest contamination with 7-bromo-3,4-dihydro-1(2H)-naphthalenone. [0091] 7-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as a yellowish-white solid (15.48 g, 35.8%); mp 69.5-75 C. (lit 74-75 C.). 1H NMR (CDCl3) corresponded to the literature description, plus a trace of heptane and an undefined by-product. TLC showed it to be cleaner than 5-bromo-3,4-dihydro-1(2H)-naphthalenone. [0092] A third fraction of orange oil (9.06 g, 20.9%) was isolated. TLC showed it to be a nearly 1:1 ratio of 5-bromo-3,4-dihydro-1(2H)-naphthalenone, and 7-bromo-3,4-dihydro-1(2H)-naphthalenone.
		Anhydrous AlCl3 (66.67 g, 0.50 mol, 99.99%) under N2 was stirred vigorously as 1-tetralone (29.83 g, 0.20 mol) was added dropwise over -7 min. The evolved HCl gas was scrubbed through 5 N NaOH. The resulting mixture was a dark brown oil that exothermed to 75 C. When the temperature had cooled to 50 C., Br2 was added dropwise over 15 min. The mixture, which had cooled further to 40 C., was heated to 80 C. for 5 min, then poured into a mixture of ice (600 g) and 12 N HCl (80 mL). All the ice melted, leaving a cool dark mixture which was diluted with H2O (200 mL) and extracted with CH2Cl2 (200 mL, 100 mL). The combined extracts were dried with MgSO4 and concentrated in vacuo (30-60 C.) to a dark brown oil (45.6 g; theory=45.02 g). Chromatography over silica gel 60 with 8:1 heptane:THF did not prove effective, but two passes through the Biotage radially pressured silica gel cartridges using 9:1 heptane:MTBE as eluent produced acceptably pure fractions. 5-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as an orange oil (12.27 g, 28.3%). HPLC showed an apparent wide divergence in absorbances at 230 nm for the two regioisomers, and was therefore not reliable for a potency check. TLC on silica gel (4:1 heptane:MTBE) confirmed modest contamination with 7-bromo-3,4-dihydro-1(2H)-naphthalenone. 7-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as a yellowish-white solid (15.48 g, 35.8%); mp 69.5-75 C. (lit 74-75 C.). 1H NMR (CDCl3) corresponded to the literature description, plus a trace of heptane and an undefined by-product. TLC showed it to be cleaner than 5-bromo-3,4-dihydro-1 (2H)-naphthalenone. A third fraction of orange oil (9.06 g, 20.9%) was isolated. TLC showed it to be a nearly 1:1 ratio of 5-bromo-3,4-dihydro-1(2H)-Naphthalenone, and 7-bromo-3,4-dihydro-1(2H)-Naphthalenone.

Reference： [1]Patent: WO2005/95326,2005,A2 .Location in patent: Page/Page column 110-111
[2]Patent: WO2004/94384,2004,A2 .Location in patent: Page 63-64
[3]Patent: WO2004/94413,2004,A1 .Location in patent: Page 63-64
[4]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 29 - 35
[5]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4405 - 4409
[6]Synthetic Communications,1994,vol. 24,p. 2777 - 2788
[7]Gazzetta Chimica Italiana,1988,vol. 118,p. 369 - 374
[8]Patent: US5753655,1998,A
[9]Patent: US2004/6229,2004,A1 .Location in patent: Page/Page column 13-14
[10]Organic and Biomolecular Chemistry,2017,vol. 15,p. 1381 - 1392
[11]Patent: US2003/225281,2003,A1 .Location in patent: Page 12

11
[ 32281-97-3 ]
[ 74-88-4 ]
[ 148925-37-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	In benzene	1 7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-one PREPARATION 1 7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-one To solution of 9.78 g (39 mmol) of 7-bromo-1,2,3,4-tetrahydronaphthalen-1-one (R. W. Griffin, J. D. Gass, M. A. Berwick, R. S. Shulman, J.Org.Chem.1964, 29 , 2109) and 6.45 mL (105 mmol) of methyl iodide in 74 mL of benzene, were added under argon atmosphere 3.71 g (77 mmol) of 55% sodium hydride. The mixture was stirred at 60°C for 5 h and then at reflux overnight. The suspension was poured into methanol and then the solvent was removed. The residue was dissolved in ether and washed with H2O and Na2CO3. The organic solution was dried over MgSO4 and the solvent was evaporated, affording a crude that was chromatographed on silica gel eluding with mixtures of hexane-CH2Cl2 of increasing polarity. 9.90 g of the product were obtained as a colorless oil (yield: 100%). IR (film) ν: 2957, 2921, 1679, 1583, 1469, 1398, 1302, 1208, 1107, 828 cmmin1; 1H NMR (80 MHz, CDCl3) δ (TMS): 8.13 (d, J= 2Hz, 1H, Ar), 7.55 (dd, Ja= 8Hz, Jb= 2Hz, 1H, Ar), 7.09 (d, J= 8Hz, 1H, Ar), 2.92 (t, J= 6.5Hz, 2H, CH2Ar), 1.96 (t, J= 6.5Hz, 2H, CH2), 1.20 (s, 6H, 2CH3).
95%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With potassium <i>tert</i>-butylate In tetrahydrofuran for 6h; Reflux; Stage #2: methyl iodide at 20 - 50℃; for 3.25h;	163.A Potassium tert-butoxide (39.88 g, 355.4 mmol) was added to a solution of 7-bromo-3,4-dihydronaphthalen-l (2H)-one (20.0 g, 88.8 mmol) in tetrahydrofuran (180 mL). The resulting brown suspension was heated to reflux for 6 hours and then cooled to room temperature. Iodomethane (44.36 mL, 710 mmol) was added dropwise by addition funnel over 15 minutes, and the reaction mixture was heated to 50°C for 3 hours and then stirred at room temperature overnight. The reaction mixture was then cooled to 0°C, water was added, and the mixture was extracted with ethyl acetate. The combined extracts were dried anhydrous sodium sulfate, filtered, and concentrated. Purification by flash column chromatography provided 7-bromo-2,2-dimethyl-3,4- dihydronaphthalen-l(2H)-one (21.4 g, 95%). 1H NMR (400 MHz, (CD3)2SO) δ 7.92 (d, J = 2.0 Hz, 1H), 7.73 (dd, J = 2.4, 8.4 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 2.93 (t, J = 6.4 Hz, 2H), 1.93 (t, J = 6.4 Hz, 2H), 1.1 1 (s, 6H).
90%	With sodium hydride In benzene Heating;

86%

Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With sodium hydride In tetrahydrofuran for 1h; Cooling with ice; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 16h;

6-Methoxy-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-one (8b) [25,27]: General procedure: To a stirred solution of6-methoxy-3,4-dihydronaphthalen-1(2H)-one 7b (10.0 g, 56.8 mmol) dissolved in dry tetrahydrofuran(THF, 150 mL) in a 500 mL round bottomed flask was added NaH (11.4 g, 284 mmol, 60% in oil).After stirring the mixture for 1 h under ice-water bath, methyl iodide (32.3 g, 227 mmol) in dryTHF (50 mL) was added slowly. The mixture was allowed to stir at r.t. for 16 h. The reactionwas quenched by addition of water (slowly and dropwise). The mixture was then extractedwith ethyl acetate (3 100 mL), washed with water (2 100 mL), and dried over anhydrousNa2SO4. Evaporation of the solvent yielded a yellow oil. The residue was subjected to silica gelchromatography using petroleum ether (PE) and ethyl acetate (EtOAc) (10:1) as eluent to afford6-methoxy-2,2-dimethyl-3,4-dihydronaphthalen-1(2H)-one 8b (10.4 g, yield 90%) as a yellow oil.

Reference： [1]Current Patent Assignee: URIACH S.A. - EP525768, 1993, A1
[2]Current Patent Assignee: ROCHE HOLDING AG - WO2011/123674, 2011, A1 Location in patent: Page/Page column 159-160
[3]Almansa; Gomez; Cavalcanti; Rodriguez; Carceller; Bartroli; Garcia-Rafanell; Forn [Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2121 - 2133]
[4]Wan, Chuan; Wang, Mingan; Yang, Dongyan; Han, Xiaoqiang; Che, Chuanliang; Ding, Shanshan; Xiao, Yumei; Qin, Zhaohai [Molecules, 2017, vol. 22, # 12]

12
[ 32281-97-3 ]
[ 58472-34-7 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With potassium <i>tert</i>-butylate; oxygen In <i>tert</i>-butyl alcohol at 25℃; for 1h; Inert atmosphere; Stage #2: With hydrogenchloride In water at 0℃; Inert atmosphere;
32%	With potassium <i>tert</i>-butylate; oxygen In <i>tert</i>-butyl alcohol at 20℃; for 2h;
	With potassium <i>tert</i>-butylate; oxygen In <i>tert</i>-butyl alcohol

1.52g (34%)		10.a a. a. 6-Bromo-3-hydroxy-1,4-naphthoquinone Autoxidation of 7-bromo-1-tetralone (4g; 0.0178 mole) as described in example 8(b) afforded 1.52g (34%) of the title compound of m.p. 197° C. Recrystallization from ethanol raised the m.p. to 216° C. (Found; C, 47.50; H, 2.12; Br, 31.43; C10 H5 BrO3 requires; C, 47.49; H, 1.99; Br, 31.60%).
	With potassium <i>tert</i>-butylate; oxygen In <i>tert</i>-butyl alcohol at 20℃;	1.1 Synthesis of 7-bromo-2-hydroxynaphthalene-1,4-dione General procedure: The procedure is the similar as described in 1.1 of Protocol I. NMR (400 MHz, DMSO-ifc) δ 8.04 (d, / = 2.1 Hz, 2H), 8.03 (d, / = 8.1 Hz, 2.1 Hz, 1H), 7.84 (d, / = 8.1 Hz, 1H), 6.16 (s, 1H). To the solution of t-BuOK (4 equivalents) in t-BuOH, ketone A (1 equivalent, commercial available or synthesized by method mentioned as following) was added in batch under oxygen atmosphere. After then the reaction mixture was stirred under oxygen atmosphere at room temperature till the TLC showed all the starting material had gone. After the mixture was poured into excess water, the mixture was washed with ethyl acetate, and then the aqueous phase was titrated with con. HC1 solution until a pH 1 was obtained. Aqueous phase was extracted with ethyl acetate three times, and the organic phase was collected. After organic phase was washed with sat. Na2C03 solution, basic aqueous phase was collected and titrated with con. HC1 solution. After extraction with ethyl acetate, the organic phase was collected, dried over MgSC , and concentrated in vacuo. Desired crude product intermediate B (R7=H) was afford as a dark red or orange solid.

Reference： [1]Lim, Sang Min; Jeong, Yujeong; Lee, Suhyun; Im, Honggu; Tae, Hyun Seop; Kim, Byung Gyu; Park, Hee Dong; Park, Jonghoon; Hong, Sungwoo [Journal of Medicinal Chemistry, 2015, vol. 58, # 21, p. 8491 - 8502]
[2]Wu, Li-Qiang; Ma, Xin; Liu, Zhao-Peng [Bioorganic Chemistry, 2021, vol. 113]
[3]Buckle; Cantello; Smith; Spicer [Journal of Medicinal Chemistry, 1977, vol. 20, # 8, p. 1059 - 1064]
[4]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4014907, 1977, A
[5]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - WO2017/106624, 2017, A1 Location in patent: Paragraph 00119; 00131

13
[ 201230-82-2 ]
[ 32281-97-3 ]
[ 71-36-3 ]
7-butoxycarbonyl-α-tetralone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With bis-triphenylphosphine-palladium(II) chloride In triethylamine; N,N-dimethyl-formamide at 80℃;

Reference： [1]Chen, Li; Trilles, Richard V.; Tilley, Jefferson, W. [Tetrahedron Letters, 1995, vol. 36, # 48, p. 8715 - 8718]

14
[ 32281-97-3 ]
[ 33513-42-7 ]
[ 283177-40-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With trichlorophosphate In Trichloroethylene at 60 - 70℃; for 6h;
	With trichlorophosphate

Reference： [1]Ray, Jayanta K.; Haldar, Manas K.; Gupta, Susmita; Kar, Gandhi K. [Tetrahedron, 2000, vol. 56, # 6, p. 909 - 912]
[2]Patra, Prasanta; Kar, Gandhi K.; Khatua, Biswajit [Journal of Heterocyclic Chemistry, 2015, vol. 51, # 5, p. 1306 - 1310]

15
[ 75-77-4 ]
[ 32281-97-3 ]
[ 309929-09-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With triethylamine at 20℃; for 0.25h; Inert atmosphere; Stage #2: chloro-trimethyl-silane for 0.666667h; Inert atmosphere; Stage #3: With sodium iodide In acetonitrile at 40℃; for 2h;	1-1 Synthesis of Compound (2) Compound (1) (270 g, 1.85 mol) and triethylamine (514 g, 5.08 mol) were added to a 2000 ml flask under argon or nitrogen atmosphere and stirred at room temperature for 15 minutes. Then, trimethylsilyl chloride (541 g, 5.08 mol) was slowly added thereto and stirred for 40 minutes. Sodium iodide (369 g, 2.46 mol) was slowly added to 2200 ml of acetonitrile so that the temperature did not exceed 40 ° C, and the mixture was stirred for 2 hours. When the reaction was completed, 3 L of cold distilled water was added and extracted twice with 1 L of pentene. After removing moisture with anhydrous sodium sulfate, the solvent was removed to obtain a brown oil compound (2) (402 g,96%).
92%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at -78 - 20℃; for 2h;
69%	With triethylamine; sodium iodide In acetonitrile at 20℃; for 0.5h; Inert atmosphere;

Reference： [1]Current Patent Assignee: DONGJIN SEMICHEM CO.,LTD. - KR2016/35562, 2016, A Location in patent: Paragraph 0083-0086
[2]Kreier; Frohlich; Wegelius; Hoppe [Synthesis, 2000, # 10, p. 1391 - 1402]
[3]Talamas, Francisco X.; Abbot, Sarah C.; Anand, Shalini; Brameld, Ken A.; Carter, David S.; Chen, Jun; Davis, Dana; De Vicente, Javier; Fung, Amy D.; Gong, Leyi; Harris, Seth F.; Inbar, Petra; Labadie, Sharada S.; Lee, Eun K.; Lemoine, Remy; Le Pogam, Sophie; Leveque, Vincent; Li, Jim; McIntosh, Joel; Nájera, Isabel; Park, Jaehyeon; Railkar, Aruna; Rajyaguru, Sonal; Sangi, Michael; Schoenfeld, Ryan C.; Staben, Leanna R.; Tan, Yunchou; Taygerly, Joshua P.; Villaseñor, Armando G.; Weller, Paul E. [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1914 - 1931]

16
[ 32281-97-3 ]
[ 676-58-4 ]
[ 35943-86-3 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran for 3h; cooling;
	In tetrahydrofuran at 0 - 20℃; for 2h;	1 Step 1:7-bromo-1-methyl-1 ,2,3,4-tctrahydronaphthalen-1 -01 To a solution of 7-bromotetralin-1-one (1.0 g, 4.44 mmol) in TI-IF (20 mL) at 0 °C was addedMeMgC1 (3 M in THF, 5.92 mL, 17.8 mmol) dropwise. The mixture was stirred at roomtemperature for 2 h. The reaction was quenched with Sat. NH4C1 and extracted with DCM (3x).The combined organic layers were dried (Na2SO4), filtered and concentrated to a yellow oil toafford the title compound (715 mg, 99.9% yield) that was used without purification. Ln NMR(400 MHz, Chloroform-ti) 6 7.71 (d, J 2.10 Hz, in), 7.29 7.23 (m, 1H), 6.94 (dt, J 1.00,8.28 Hz, 1H), 3.77-3.69 (m, 1H), 2.72 (q, J = 6.25, 7.13 Hz, 2H), 1.95- 1.79 (m, 4H).

Reference： [1]Singh, Ishwar; Seitz, Oliver [Organic Letters, 2006, vol. 8, # 19, p. 4319 - 4322]
[2]Current Patent Assignee: MORPHOSYS AG; ROCHE HOLDING AG - WO2016/112284, 2016, A1 Location in patent: Page/Page column 84; 85

17
[ 32281-97-3 ]
[ 105-58-8 ]
[ 914262-72-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: Diethyl carbonate With sodium hydride In benzene at 65℃; Stage #2: 7-bromo-3,4-dihydro-2H-naphthalen-1-one In benzene for 3h; Heating;
77%	With sodium hydride In toluene; oil at 65 - 80℃; for 3.83333h;	31.A Intermediate ethyl 7-bromo-l-oxo- 1 ,2,3, 4-tetrahydronaphthalene-2- carboxylate was prepared in a similar fashion to Chackal-Catoen, Sarah, et al. "Dicationic DNA-targeted antiprotozoal agents: Naphthalene replacement of benzimidazole." Biorg. Med. Chem., 14(22) (2006): pp. 7434-7445. Diethyl carbonate (21.5 mL, 178 mmol) was added to a suspension of 60% (oil dispersion) sodium hydride (2.67 g, 66.6 mmol) in dry toluene (50 mL) under nitrogen. No exotherm was observed. This mixture was heated to 65 °C, and a solution of 7-bromo-3,4-dihydronaphthalen-l(2H)-one (5.0 g, 22 mmol) in dry toluene (25 mL) was added dropwise over a period of 20 minutes. After the addition was completed, the mixture was heated to 80°C. The reaction became quite thick after 30 minutes, so more toluene (100 mL) was added to ensure stirring. The mixture was stirred for 3 hours at 80°C. After cooling in an ice bath, acetic acid (5 mL) was added dropwise. The mixture was carefully added to an Erlenmeyer flask containing ice under a blanket of N2 and stirred for 30 minutes. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with ice-cold water (50 mL), brine (50 mL), dried (MgS04), filtered, and concentrated. The resulting solid was triturated with absolute ethanol (20 mL), and the solid was filtered (3.9 g). The mother liquor was concentrated, and the residue was triturated a second time with absolute EtOH (5 mL). The second crop was filtered, giving ethyl 7-bromo-l-oxo-l ,2,3,4-tetrahydronaphthalene-2- carboxylate (5.2 g, 77% yield).

Reference： [1]Chackal-Catoen, Sarah; Miao, Yi; Wilson, W. David; Wenzler, Tanja; Brun, Reto; Boykin, David W. [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 22, p. 7434 - 7445]
[2]Current Patent Assignee: ROCHE HOLDING AG - WO2011/123674, 2011, A1 Location in patent: Page/Page column 80-81

18
[ 16982-21-1 ]
[ 32281-97-3 ]
[ 1017589-76-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one; diazomethyl-trimethyl-silane With diethylaluminium chloride In hexane; dichloromethane at 0 - 20℃; for 0.416667h; Stage #2: With phenyltrimethylammonium tribromide In tetrahydrofuran at 0 - 20℃; for 1.25h; Stage #3: ethyl 2-amino-2-thioxoacetate In ethanol at 20℃;	161 Into a solution of 7-bromo-3,4-dihydronaphthalen-l(2H)-one (4.5Og, 20.0mmol) in methylene chloride (200 niL) at O0C was added a solution of IM diethylaluminum chloride in hexane (22.0 mL, 22.0 mmol). Into the reaction mixture a solution of 2.0M trimethylsilyldiazomethane (11.0 mL, 22.0 mmol) was added slowly. The mixture was stirred at O0C for 15 minutes then at room temperature for 10 minutes. Ice was added. The resulting mixture was acidified with a solution of 3N HCl, extracted with methylene chloride (2X). The combined extracts were washed with a solution of saturated NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was taken in THF (100 mL). The mixture was cooled to O0C. Into the reaction mixture, phenyltrimethylamonium tribromide (7.52g, 20.0 mmol) was added. The mixture was stirred at O0C for 15 minutes then at room temperature for 1 hour. The reaction mixture was quenched by addition of a solution of 10% NaHSO3, stirred at room temperature for 10 minutes, extracted with methylene chloride. The extract was washed with water, dried (Na2SO4), filtered and concentrated. The residue was taken in ethanol (20.0 mL). Into the mixture, ethyl thiooxamate (2.66g, 20.0 mmol) was added. The mixture was stirred at room temperature overnight, neutralized with a solution of saturated NaHCO3, extracted with methylene chloride (2X). The combined extracts were dried (Na2SO4), filtered and concentrated. The residue was purified on silica gel to give 161a (3.45g). MS (ESI) [M+H+]: 354, 352.

Reference： [1]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2008/39520, 2008, A2 Location in patent: Page/Page column 158

19
[ 32281-97-3 ]
[ 100-52-7 ]
[ 116047-27-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium hydroxide In methanol at 20℃; for 48h;
91%	With potassium hydroxide In methanol; water at 20℃; for 12h;

Reference： [1]Xu, Wen-Zhi; Huang, Zhi-Tang; Zheng, Qi-Yu [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5606 - 5608]
[2]Korenaga, Toshinobu; Kosaki, Takahiro; Kawauchi, Yusuke; Ema, Tadashi; Sakai, Takashi [Journal of Fluorine Chemistry, 2006, vol. 127, # 4-5 SPEC. ISS., p. 604 - 609]

20
[ 6340-79-0 ]
[ 32281-97-3 ]

Reference： [1]Canadian Journal of Chemistry,2006,vol. 84,p. 1487 - 1503
[2]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7434 - 7445
[3]Journal of the American Chemical Society,2001,vol. 123,p. 3940 - 3952
[4]Journal of Organic Chemistry,1992,vol. 57,p. 366 - 370
[5]Journal of the American Chemical Society,1938,vol. 60,p. 170,174
[6]Journal of Organic Chemistry,1964,vol. 29,p. 2109 - 2116
[7]Bulletin de la Societe Chimique de France,1971,p. 2092 - 2094
[8]Advanced Synthesis and Catalysis,2018,vol. 360,p. 2894 - 2899
[9]Journal of Heterocyclic Chemistry,2019,vol. 56,p. 1672 - 1683
[10]Organic Letters,2019,vol. 21,p. 7179 - 7183

21
[ 32281-97-3 ]
{7-[2-Amino-2-(dimethoxy-phosphoryl)-ethyl]-naphthalen-1-yl}-acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 1.) LDA / 1.) THF, hexane, -78 deg C, 15 min, 2.) THF, hexane, from -78 to -25 deg C, 2.5 h 2: p-TsOH*H₂O / benzene / 1.5 h / Heating 3: 1.) Br₂, 2.) DBU / 1.) CCl₄, 25 deg C, 2 h, 2.) benzene, 25 deg C, 12 h 4: 82 percent / Pd(PPh₃)4 / benzene / 15 h / Heating 5: 67 percent / OsO₄, N-methylmorpholine N-oxide / acetone; H₂O / 17 h 6: aq. NaIO₄ / diethyl ether / 1.25 h / 25 °C 7: glacial AcOH / 1.5 h / 25 - 90 °C 8: K₂CO₃ / 2.75 h / 25 °C 9: 154 mg / H₂ / 5percent Pd/C / methanol / 3.5 h / 25 °C

Reference： [1]Meyer, J. Hoyt; Bartlett, Paul A. [Journal of the American Chemical Society, 1998, vol. 120, # 19, p. 4600 - 4609]

22
[ 32281-97-3 ]
[ 208169-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1: 1.) LDA / 1.) THF, hexane, -78 deg C, 15 min, 2.) THF, hexane, from -78 to -25 deg C, 2.5 h 2: p-TsOH*H₂O / benzene / 1.5 h / Heating 3: 1.) Br₂, 2.) DBU / 1.) CCl₄, 25 deg C, 2 h, 2.) benzene, 25 deg C, 12 h 4: 82 percent / Pd(PPh₃)4 / benzene / 15 h / Heating 5: 67 percent / OsO₄, N-methylmorpholine N-oxide / acetone; H₂O / 17 h 6: aq. NaIO₄ / diethyl ether / 1.25 h / 25 °C 7: glacial AcOH / 1.5 h / 25 - 90 °C 8: K₂CO₃ / 2.75 h / 25 °C 9: 154 mg / H₂ / 5percent Pd/C / methanol / 3.5 h / 25 °C 10: 70 percent / HOBt, EDC / CH₂Cl₂ / 0 - 25 °C 11: 89 percent / aq. LiOH / methanol / 2.25 h / 25 °C

Reference： [1]Meyer, J. Hoyt; Bartlett, Paul A. [Journal of the American Chemical Society, 1998, vol. 120, # 19, p. 4600 - 4609]

23
[ 32281-97-3 ]
[ 208169-43-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 1.) LDA / 1.) THF, hexane, -78 deg C, 15 min, 2.) THF, hexane, from -78 to -25 deg C, 2.5 h 2: p-TsOH*H₂O / benzene / 1.5 h / Heating 3: 1.) Br₂, 2.) DBU / 1.) CCl₄, 25 deg C, 2 h, 2.) benzene, 25 deg C, 12 h 4: 82 percent / Pd(PPh₃)4 / benzene / 15 h / Heating 5: 67 percent / OsO₄, N-methylmorpholine N-oxide / acetone; H₂O / 17 h 6: aq. NaIO₄ / diethyl ether / 1.25 h / 25 °C 7: glacial AcOH / 1.5 h / 25 - 90 °C 8: K₂CO₃ / 2.75 h / 25 °C 9: 154 mg / H₂ / 5percent Pd/C / methanol / 3.5 h / 25 °C 10: 70 percent / HOBt, EDC / CH₂Cl₂ / 0 - 25 °C

Reference： [1]Meyer, J. Hoyt; Bartlett, Paul A. [Journal of the American Chemical Society, 1998, vol. 120, # 19, p. 4600 - 4609]

24
[ 32281-97-3 ]
[ 208169-47-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1: 1.) LDA / 1.) THF, hexane, -78 deg C, 15 min, 2.) THF, hexane, from -78 to -25 deg C, 2.5 h 2: p-TsOHH₂O / benzene / 1.5 h / Heating 3: 1.) Br₂, 2.) DBU / 1.) CCl₄, 25 deg C, 2 h, 2.) benzene, 25 deg C, 12 h 4: 82 percent / Pd(PPh₃)4 / benzene / 15 h / Heating 5: 67 percent / OsO₄, N-methylmorpholine N-oxide / acetone; H₂O / 17 h 6: aq. NaIO₄ / diethyl ether / 1.25 h / 25 °C 7: glacial AcOH / 1.5 h / 25 - 90 °C 8: K₂CO₃ / 2.75 h / 25 °C 9: 154 mg / H₂ / 5percent Pd/C / methanol / 3.5 h / 25 °C 10: 70 percent / HOBt, EDC / CH₂Cl₂ / 0 - 25 °C 11: 89 percent / aq. LiOH / methanol / 2.25 h / 25 °C 12: 152 mg / EDCHCl / CH₂Cl₂ / 10 h / 25 °C

Reference： [1]Meyer, J. Hoyt; Bartlett, Paul A. [Journal of the American Chemical Society, 1998, vol. 120, # 19, p. 4600 - 4609]

25
[ 32281-97-3 ]
[ 1680-51-9 ]

Reference： [1]Journal of Organic Chemistry,1984,vol. 49,p. 4226 - 4237

26
[ 32281-97-3 ]
[ 51934-39-5 ]

Reference： [1]Journal of Organic Chemistry,1962,vol. 27,p. 76 - 78

27
[ 529-34-0 ]
None [ No CAS ]
[ 32281-97-3 ]
[ 68449-30-9 ]

Yield	Reaction Conditions	Operation in experiment
1: 28.3% 2: 35.8% 3: 20.9%	Stage #1: 3,4-dihydronaphthalene-1(2H)-one With aluminum (III) chloride Under N₂; Stage #2: With bromine at 80℃; for 0.0833333h;	I Preparation of 1-Bromo-5-methoxy-naphthalene; Preparation of 5-Bromo-3,4-dihydro-1(2H)-naphthalenone and 7-Bromo-3,4-dihydro-1(2H)-naphthalenone Anhydrous AlCl3 (66.67 g, 0.50 mol, 99.99%) under N2 was stirred vigorously as 1-tetralone (29.83 g, 0.20 mol) was added dropwise over 7 min. The evolved HCl gas was scrubbed through 5 N NaOH. The resulting mixture was a dark brown oil that exothermed to 75° C. When the temperature had cooled to 50° C., Br2 was added dropwise over 15 min. The mixture, which had cooled further to 40° C., was heated to 80° C. for 5 min, then poured into a mixture of ice (600 g) and 12 N HCl (80 mL). All the ice melted, leaving a cool dark mixture which was diluted with H2O (200 mL) and extracted with CH2Cl2 (200 mL, 100 mL). The combined extracts were dried with MgSO4 and concentrated in vacuo (30-60° C.) to a dark brown oil (45.6 g; theory=45.02 g).[0085] Chromatography over silica gel 60 with 8:1 heptane:THF did not prove effective, but two passes through the Biotage radially pressured silica gel cartridges using 9:1 heptane:MTBE as eluent produced acceptably pure fractions. [0086] 5-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as an orange oil (12.27 g, 28.3%). HPLC showed an apparent wide divergence in absorbances at 230 nm for the two regioisomers, and was therefore not reliable for a potency check. TLC on silica gel (4:1 heptane:MTBE) confirmed modest contamination with 7-bromo-3,4-dihydro-1(2H)-naphthalenone. [0087] 7-Bromo-3,4-dihydro-1(2H)-naphthalenone was isolated as a yellowish-white solid (15.48 g, 35.8%); mp 69.5-75° C. (lit 74-75° C.). 1H NMR (CDCl3) corresponded to the literature description, plus a trace of heptane and an undefined by-product. TLC showed it to be cleaner than 5-bromo-3,4-dihydro-1(2H)-naphthalenone. [0088] A third fraction of orange oil (9.06 g, 20.9%) was isolated. TLC showed it to be a nearly 1:1 ratio of 5-bromo-3,4-dihydro-1(2H)-naphthalenone, and 7-bromo-3,4-dihydro-1(2H)-naphthalenone.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US2003/232833, 2003, A1 Location in patent: Page 12

28
[ 32281-97-3 ]
[ 676133-23-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With dimethylsulfide borane complex In tetrahydrofuran; toluene at -25 - -15℃; for 6.3h; 4A molecular sieves;	7 Example 7. (R)-7-BROMOTETRALIN-L-OL (see note 8) 7-BROMO-L-TETRALONE (8.28 g, 36.8 mmol) was placed in a 250 mL round bottomed flask and dissolved in anhydrous THF (100 mL). Activated 4A molecular sieves were added and the mixture was aged for 5 h before transferring via cannula to a 500 ml three- necked round bottom flask fitted with a dropping funnel, thermometer, and a nitrogen inlet. The solution was cooled to- 25 °C and 1M (S)-TETRAHYDRO-L-METHYL-3, 3-DIPHENYL-LH, 3H- pyrollo [1, 2-c] [1, 3,2] oxazaborole in toluene (3.7 mL, 3.7 mmol, notes 9 and 10) was added. The dropping funnel was charged with a solution of borane- methylsulfide (1.96 g, 2.44 mL, 25.8 mmol) in anhydrous THF (45 mL, dried over 4A sieves). The borane solution was added dropwise over 20 min keeping the reaction temperature less than - 20 °C. The mixture was stirred for 1 h at-15 to-20 °C whereupon TLC analysis indicated consumption of the ketone. The reaction was quenched by careful addition of methanol (50 mL) at - 20 °C and allowed to warm to ambient temperature and stir for 16h. The volatiles were removed in vacuo and the residue was purified by silica gel chromatography (Biotage Flash 65, elution solvent 6/1 hexanes: ethyl acetate) to yield (R)-7-bromotetralin- L-OL (8.18 g, 98%, notes 11 and 12). [Note 8. Procedure adapted from: Jones, T. K.; Mohan, J. J.; Xavier, L. C.; Blacklock, T. J.; Mathre, D. J.; Sohar, P.; Turner-Jones, E. T.; Reamer, R. A.; Roberts, F. E.; Grabowski, E. J. J. J. ORG. Chem. 1991, 56, 763-769. Note 9. Source: Aldrich cat. No. 45, 770-1," (S)-2-METHYL- CBS-oxazaborolidine". Use of the S-AUXILLIARY produces R- alcohols. Note 10. The reference in note 1 indicates that use of 5 mol% oxazaborolidine catalyst gives comparable results. Note 11. Analytical chiral HPLC indicated a 98: 2 mixture of enantiomers (Chirocel OD-H column, isocratic elution 2: 98 IPA/hexane, 0.9 mL/min, RT 18.4 min (minor enantiomer), 19.5 min (major enantiomer). Note 12. Proton NMR was consistent with that previously reported for the racemate: Saito, M.; Kayama, Y.; Watanabe, T.; Fukushima, H.; Hara, T. J. Med. Chem. 1980,23, 1364-1372].
98%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one In tetrahydrofuran; toluene at -25 - -15℃; for 1.33333h; Stage #2: With methanol In tetrahydrofuran; toluene at -20 - 20℃; for 16h;	7 Example 7. (R)-7-BROMOTETRALIN-L-OL (see note 8) 7-BROMO-L-TETRALONE (8.28 g, 36.8 mmol) was placed in a 250 mL round bottomed flask and dissolved in anhydrous THF (100 ML). Activated 4A molecular sieves were added and the mixture was aged for 5 h before transferring via cannula to a 500 ml three- necked round bottom flask fitted with a dropping funnel, thermometer, and a nitrogen inlet. The solution was cooled to- 25 °C and 1M (S)-TETRAHYDRO-L-METHYL-3, 3-DIPHENYL-LH, 3H- pyrollo [1, 2-C] [1, 3,2] oxazaborole in toluene (3.7 mL, 3.7 mmol, notes 9 and 10) was added. The dropping funnel was charged with a solution of borane- methylsulfide (1.96 g, 2.44 mL, 25.8 mmol) in anhydrous THF (45 mL, dried over 4A sieves). The borane solution was added dropwise over 20 min keeping the reaction temperature less than - 20 °C. The mixture was stirred for 1 h at-15 to-20 °C whereupon TLC analysis indicated consumption of the ketone. The reaction was quenched by careful addition of methanol (50 mL) at - 20 °C and allowed to warm to ambient temperature and stir for 16h. The volatiles were removed in vacuo and the residue was purified by silica gel chromatography (Biotage Flash 65, elution solvent 6/1 hexanes: ethyl acetate) to yield (R)-7-bromotetralin- L-OL (8.18 g, 98%, notes 11 and 12). [Note 8. Procedure adapted from: Jones, T. K.; Mohan, J. J. ; Xavier, L. C.; Blacklock, T. J.; Mathre, D. J.; Sohar, P.; Turner-Jones, E. T.; Reamer, R. A.; Roberts, F. E.; Grabowski, E. J. J. J. Org. Chem. 1991, 56, 763-769. Note 9. Source: Aldrich cat. No. 45, 770-1," (S)-2-METHYL- CBS-OXAZABOROLIDINE". Use of the S-auxilliary produces R- alcohols. Note 10. The reference in note 1 indicates that use of 5 mol% oxazaborolidine catalyst gives comparable results. Note 11. Analytical chiral HPLC indicated a 98: 2 mixture of enantiomers (Chirocel OD-H column, isocratic elution 2: 98 IPA/hexane, 0.9 mL/min, RT 18.4 min (minor enantiomer), 19.5 min (major enantiomer). Note 12. Proton NMR was consistent with that previously reported for the racemate: Saito, M.; Kayama, Y.; Watanabe, T.; Fukushima, H.; Hara, T. J. Med. Chem. 1980,23, 1364-1372].
98%	With hydrogen; C₄₃H₄₅ClN₄Ru; sodium t-butanolate In isopropyl alcohol at 22℃; for 24h; Autoclave; enantioselective reaction;

95 % ee

With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; water; sodium formate; (R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine for 0.5h; Milling; enantioselective reaction;

Reference： [1]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY; PFIZER INC - WO2004/94384, 2004, A2 Location in patent: Page 67-68
[2]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY; PFIZER INC - WO2004/94413, 2004, A1 Location in patent: Page 67-68
[3]Daniliuc, Constantin G.; Glorius, Frank; Hellmann, Lars; Li, Wei; Mück-Lichtenfeld, Christian; Neugebauer, Johannes; Wagener, Tobias [Journal of the American Chemical Society, 2020, vol. 142, # 15, p. 7100 - 7107]
[4]Kolcsár, Vanessza Judit; Szőllősi, György [ChemCatChem, 2022, vol. 14, # 3]

29
[ 529-34-0 ]
[ 32281-97-3 ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: 3,4-dihydronaphthalene-1(2H)-one at 0 - 90℃; for 0.916667h; Stage #2: With bromine at 90℃; for 1h;	III 7-Bromo-1-tetralone. (Cornelius, L. A. H.; Combs, D. W. Synthetic Communications 1994, 24(19), 2777-2788) Into a round bottom flask kept at 0° C., AlCl3 (19.6 g, 146.8 mmol) was added and the reaction system was put under nitrogen. 8 mL of tetralone (8.62 g, 58.9 mmol) were added during a 10-minute period, at which point, the reaction mixture was heated in an oil bath at 90° C. for about 45 minutes before adding 3.6 mL of Br2 (11.2 g, 70.1 mmol). The reaction mixture was stirred at 90° C. for an hour before 30 mL of ice-water and 20 mL of NaHCO3 were added. The product was extracted twice from the aqueous phase with Et2O and, the resultant organic phase was washed once with NaHCO3, once with brine and dried under Na2SO4. The crude reaction mixture was purified by flash chromatography (2.5% EtOAc/97.5% hex) which afforded 5.36 g (23.8 mmol) of the product in a 40% yield. 1H NMR (300 MHz, CDCl3, δ): 8.14 (d, J=2.2, Ar, 1H), 7.56 (dd, J=8.1, 2.2, Ar, 1H), 7.13 (d, J=8.2, Ar, 1H), 2.90 (t, J=6.1, C2, 2H), 2.64 (dd, J=5.7, 5.5, C2, 2H), 2.12 (td, J=12.7, 6.4, C2, 2H). Dept 135 NMR (75 MHz, CDCl3): δ 136.1 (H), 130.7 (H), 130.0 (H), 38.8 (H2), 29.2 (H2), 23.1 (H2). EIMS: m/z (% rel. intensity) 226 (M++2, 100), 224 (M+, 100), 211 (25), 209 (25), 198(75), 196 (75), 170 (60), 168 (60), 145 (25), 115 (45), 89 (58), 63 (28).
	With bromine

Reference： [1]Current Patent Assignee: BAYLOR UNIVERSITY - US2009/76076, 2009, A1 Location in patent: Page/Page column 20
[2]Current Patent Assignee: ABBVIE INC - US2005/4213, 2005, A1 Location in patent: Page 13

30
Tebbe's reagent [ No CAS ]
[ 32281-97-3 ]
[ 740842-57-3 ]

Yield	Reaction Conditions	Operation in experiment
54%	In tetrahydrofuran; toluene at 0℃; for 3h;	5.A 7-BROMO-1-METHYLENE-1, 2, 3, 4-TETRAHYDRO-NAPHTHALENE (STEP-I, V-2) 7-Bromo-3, 4-DIHYDRO-2H-NAPHTHALEN-L-ONE (1.62 g, 7.2 mmol) was dissolved in tetrahydrofuran (18 mL) and cooled to 0 C. To it Tebbe reagent (0.5 M in toluene, 18 mL, 9 mmol) was added slowly and the reaction was stirred for 3 hours at 0 C. The reaction was quenched with 0. 1N sodium hydroxide by drop wise addition. Diluted with ethyl acetate, organic layer was separated and dried over sodium sulfate. The crude material was purified by flash silica gel chromatography to afford the title compound (Yield: 54%). LC-MS m/z: 225 (M+H).
54%	In tetrahydrofuran; toluene at 0℃; for 3h;	11.I 7-BROMO-1-METHYLENE-1, 2, 3, 4-TETRAHYDRO-NAPHTHALENE (XI-2, STEP I) : 7-Bromo-3, 4-dihydro-2H-naphthalen-1-one (1.62 g, 7.2 mmol) was dissolved in tetrahydrofuran (18 mL) and cooled to 0 C. To this solution was slowly added Tebbe's reagent (0.5 M in toluene, 18 mL, 9 mmol), and the reaction mixture was stirred for 3 hours at 0 C. The reaction was quenched with 0. 1N sodium hydroxide by drop wise addition. Ethyl acetate was added, and the organic layer was separated, dried over sodium sulfate, and concentrated. The crude material was purified by flash silica gel chromatography to afford the title compound (Yield: 54%). LC-MS m/z: 225 (M+H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/69244, 2004, A1 Location in patent: Page/Page column 82; 83
[2]Current Patent Assignee: PFIZER INC - WO2004/69832, 2004, A2 Location in patent: Page 110-111

31
[ 32281-97-3 ]
[ 411235-57-9 ]
[ 845672-34-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; water In toluene at 100℃; for 1h;	88.a a) 7-CYCLOPROPYL-3, 4-DIHYDRO-2H-NAPHTHALEN-1-ONE; To a yellow suspension of 2 g 7-BROMO-1-TETRALONE, 1 g boronic acid, 7.1 g potassium phosphate (pulverized) and 0.28 g tricyclohexylphosphine in 40 ml toluene and 2 ml water 0.1 g of palladium acetateis added under a argon atmosphere. The mixture is heated to 100°C. After 1 h, the reaction mixture is allowed to cool to rt and quenched with water. The reaction mixture is extracted with EtOAc. The combined organic phases are washed with brine, dried over sodium sulfate and filtered. The brown oil is purified by flash- chromatography (hexane/EtOAc = 6/1). MS (ESI+) : 187 [M+H]

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2005/14517, 2005, A2 Location in patent: Page/Page column 38

32
[ 32281-97-3 ]
[ 68449-30-9 ]
[ 345995-26-8 ]
[ 148378-71-6 ]
[ 345995-25-7 ]

Yield	Reaction Conditions	Operation in experiment
9.4%; 79.4%	With hydrogenchloride; bromine; In diethyl ether; dichloromethane; at -5℃; for 2h;	Preparation of 2,5-Dibromo-3,4-dihydro-1(2H)-naphthalenone. [0094] A clear yellow solution of <strong>[68449-30-9]5-bromo-3,4-dihydro-1(2H)-naphthalenone</strong>(12.09 g, 53.7 mmol) in freshly opened Et2O (220 mL) under an N2 atmosphere was chilled to -5 C. HCl was bubbled in subsurface for 1 min, causing no visible change. The dropwise addition of a solution of Br2 (8.58 g, 53.7 mmol) in CH2Cl2 (20 mL) and Et2O (2 mL) to the vigorously stirring solution of <strong>[68449-30-9]5-bromo-3,4-dihydro-1(2H)-naphthalenone</strong> over 2 h (each drop was allowed to fully decolorize before adding the next) produced a product mixture that assayed by HPLC. Peak area showed 79.4% title compound, 9.5% unreacted <strong>[68449-30-9]5-bromo-3,4-dihydro-1(2H)-naphthalenone</strong>, 0.6% unidentified, and 9.4% 2,2',5-tribromo-1-tetralone. The addition of H2O produced a top light brown organic phase, and a clear, colorless bottom aqueous phase which was separated. After drying with MgSO4, the organic layer was concentrated in vacuo at room temperature to give the crude intermediate title compound as a light brown oil (16.08 g, 98.5%).

Reference： [1]Patent: US2004/6229,2004,A1 .Location in patent: Page/Page column 14

34
[ 32281-97-3 ]
[ 91270-69-8 ]

Yield	Reaction Conditions	Operation in experiment
56%		Step D: A solution of tetrabutylammonium tribromide (11.8 g, 24.4 mmol) in dichloromethane (80 ml) was added dropwise to a solution of the product from Step C (5.0 g, 22.2 mmol) in dichloromethane (20 ml) and methanol (20 ml) at room temperature over 1 hour. At completion of the addition, the mixture was stirred at room temperature for 15 hours and was then concentrated. The residue was taken into dichloromethane and was washed with saturated sodium bicarbonate three times. The organic layer was concentrated and the residue was dissolved in dimethylformamide (100 ml). Lithium carbonate (5.3 g, 71.1 mmol) and lithium bromide (4.1 g, 46.6 mmol) were added and the resulting mixture was stirred at 140° C. for 1.5 hours. After cooling to room temperature, the solids were filtered and rinsed with ethyl acetate. The filtrate was washed with water four times and dried over sodium sulfate to give 7-bromonaphthalen-1-ol (2.7 g, 56percent): 1H NMR (300 MHz, CDCl3) delta 8.41 (d, J=1.8 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.57 (dd, J=8.7, 1.8 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.28-7.35 (m, 1H), 6.62 (d, J=7.2 Hz, 1H), 5.80 (br s, 1H).

Reference： [1]Patent: US2006/52378,2006,A1 .Location in patent: Page/Page column 113
[2]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 1199 - 1203

35
[ 109-04-6 ]
[ 32281-97-3 ]
(+)-7-Bromo-1-hydroxy-1-(pyridin-2-yl)-1,2,3,4-tetrahydronaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; n-butyllithium In hexane	R.1 (+-) -7-Bromo-1-hydroxy-1-(2-pyridyl)-1,2,3,4-tetrahydronaphthalene REFERENCE EXAMPLE 1 (+-) -7-Bromo-1-hydroxy-1-(2-pyridyl)-1,2,3,4-tetrahydronaphthalene To a solution of 54.2 mL (0.088 mol) of n-BuLi 1.6m in hexane was added at -45 °C a solution of 7.20 mL (0.076 mol) of 2-bromopyridine in 33 mL of anhydrous ether and the mixture was stirred under an argon atmosphere for 10 min. 16.44 g (0.073 mol) of 7-bromo-1,2,3,4-tetrahydronaphthalen-1-one (R. W. Griffin, J. D. Gass, M. A. Berwick, R. S. Shulman, J. Org. Chem.,1964, 29, 2109) in 100 mL of anhydrous ether was added and the mixture was stirred at -30°C for 2 h. The mixture was then allowed to warm up to room temperature. 50 mL of 1N HCl was added and the layers were separated. The organic phase was extracted with 1N HCl and the combined aqueous phases were basified with 1N NaOH. The precipitate thus obtained was filtered and dried, to afford 15.27 g of a white solid (yield: 69%). A sample was purified by chromatography on silica gel (CH2Cl2-hexane) to give the analytically pure product. M.p.: 119-120°C; IR (KBr) v: 3500-3100, 2938, 1583, 1467, 1427, 1405, 1177, 1020, 786 cmmin1; 1H-RMN (80MHz, CDCl3) δ (TMS): 8.57 (d, J=5Hz, 1H, pyr), 7.61 (t of d, J=8Hz, J=1.6Hz, 1H, Ar), 7.4-6.9 (m, 5H, Ar), 5.85 (s, 1H, OH), 2.9 (m, 2H, CH2Ar), 2.0 (m, 4H, 2CH2); Analysis Calcd. for C15H14BrNO: C 59.23%; H 4.64%, N 4.60%. Found: C 59.23%; H 4.70%; N 4.54%.
	With hydrogenchloride; n-butyllithium In hexane	R.1 (+)-7-Bromo-1-hydroxy-1-(2-pyridyl)-1,2,3,4-tetrahydronaphthalene REFERENCE EXAMPLE 1 (+)-7-Bromo-1-hydroxy-1-(2-pyridyl)-1,2,3,4-tetrahydronaphthalene To a solution of 54.2 mL (0.088 mol) of n-BuLi 1.6 m in hexane was added at -45° C. a solution of 7.20 mL (0.076 mol) of 2-bromopyridine in 33 mL of anhydrous ether and the mixture was stirred under an argon atmosphere for 10 min. 16.44 g (0.073 mol) of 7-bromo-1,2,3,4-tetrahydronaphthalen-1-one (R. W. Griffin, J. D. Gass, M. A. Berwick, R. S. Shulman, J. Org. Chem., 1964, 29, 2109) in 100 mL of anhydrous ether was added and the mixture was stirred at -30° C. for 2 h. The mixture was then allowed to warm up to room temperature. 50 mL of 1N HCl was added and the layers were separated. The organic phase was extracted with 1N HCl and the combined aqueous phases were basified with 1N NaOH. The precipitate thus obtained was filtered and dried, to afford 15.27 g of a white solid (yield: 69%). A sample was purified by chromatography on silica gel (CH2 Cl2 -hexane) to give the analytically pure product. M.p.: 119°-120° C.; IR (KBr) v: 3500-3100, 2938, 1583, 1467, 1427, 1405, 1177, 1020, 786 cm-1;

Reference： [1]Current Patent Assignee: URIACH S.A. - EP600147, 1994, A1
[2]Current Patent Assignee: URIACH S.A. - US5356915, 1994, A

36
[ 860625-20-3 ]
[ 32281-97-3 ]
[ 1201375-81-6 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; water at 160℃; for 0.5h; Microwave irradiation;	34 Example 34: 3-ri-(ethylsulfonvϖ-4-piperidinvϖ-5-{8-r(2-methvIprøpyl)amino1-5,6,7,8- tetrahvdro-2-naphthalenyl)-1 H-indole-7-carboxamide trifluoroacetate;To a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 H-indole-7-carboxamide (200 mg, 0.434 mmol) in dioxane (3.0 mL) and H2O (1.0 mL) was added 7-bromo-3,4-dihydro-1 (2H)-naphthalenone (292 mg, 1.30 mmol), and potassium carbonate (360 mg, 2.60 mmol) in a microwave tube. The reaction mixture was degassed for 5 min before the addition of tetrakis (triphenylphosphosphine) palladium (0) (50 mg, 0.043 mmol). The reaction was then heated in the microwave for 30 min at 1609 C. The reaction was then filtered and the solid was dissolved in EtOAc and H2O. The organic layer was separated and concentrated. The crude residue was purified by Gilson Preparatory HPLC to yield 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(8-oxo- 5,6,7,8-tetrahydro-2-naphthalenyl)-1 H-indole-7-carboxamide.

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2007/5534, 2007, A2 Location in patent: Page/Page column 107

37
[ 32281-97-3 ]
[ 885953-12-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium azide; sulfuric acid In toluene at 0 - 20℃;
75%	With sodium azide; sulfuric acid In toluene at 0 - 20℃; for 16.5h; Inert atmosphere;	22 8-Bromo-l,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one: To a stirring solution of 7-bromotetralin-l-one, (11.30 g, 50.2 mmol, 1 eq) in 100 mL of dry toluene at rt under nitrogen in a two necked round bottom flask, equipped with an addition funnel, was added sodium azide (13.06 g, 200.8 mmol, 4 eq) in one portion. The solution was cooled to 0 °C in and concentrated sulfuric acid, (12.55 mL, 150.6 mmol, 3 eq) was added dropwise over 0.5 h via an addition funnel. The reaction was warmed to rt and stirred for 16 h. The reaction was slowly quenched by the addition of sat aq NaHCCh solution, allowing off gassing to occur and avoid overflow. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (100 mL x 3). Combined organic layers were washed with sat aq NaHCCh solution (75 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The dark brown solid/sludge was suspended with 25 mL of diethyl ether, stirred for 15 minutes, filtered, and rinsed with an additional 25 mL of diethyl ether. The resulting light tan was dried and used without further purification as 8- bromo-l,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one (9.0 g, 75 % yield, m/z: 240 [M+H]+ observed). 1H MR (400 MHz, CDCb): d 8.11 (s, 1H), 7.26 (dd, J= 8.0, 2.0 Hz, 1H), 7.16 (d, J= 2.0 Hz, 1H), 7.09 (d, 7= 8.1 Hz, 1H), 2.76 (t, J= 7.2 Hz, 2H), 2.36 (tt, J= 7.3, 1.0 Hz, 2H), 2.23 (pd, J= 7.3, 1.2 Hz, 2H).
66%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With hydroxylamine hydrochloride; sodium methylate In methanol at 60℃; for 20h; Stage #2: With PPA at 130℃; for 0.2h;	4.A SYNTHETIC PREPARATION 4; Synthesis of 8-bromo-7-(6-hydroxybenzo[d][1 ,3]dioxol-5-yl)-1 ,2,3,4- tetrahydroazepino[3,2, 1 -/7/]indol-6(7H)-oneA. Synthesis of 8-bromo-4,5-dihydro-1H-benzofιb1azepin-2(3H)-one A mixture of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (10.0 g, 44.0 mmol) , hydroxylamine hydrochloride (3.2 g, 45.0 mmol) and sodium methoxyde (2.4 g, 45.0 mmol) in methanol (100 mL) was stirred at 60 0C for 20 hours. After completion of the reaction, methanol was distilled off under reduced pressure and the residue was washed with water and filtered. The solid (7.4 g, 31 mmol) was heated at 130 0C with polyphosphoric acid (100 g) under inert atmosphere for 12 minutes and poured hot onto crashed ice (400 g). The solid residue was filtered off and recrystallized from ethanol (100 ml) to afford 8-bromo-4,5-dihydro-1/-/-benzo[t>]azepin-2(3/-/)-one (4.9 g, 66%) as a white powder: MS (ES+) m/z 240.1 , 242.1 (M + 1 ).

		65.1 Step 1: Borane tetrahydrofuran complex (1 M solution in tetrahydrofuran, 21 mL, 21 mmol) was added to a solution of 8-bromo-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (prepared from 7-bromo-3,4-dihydro-2H-naphthalen-1-one in analogy with the general procedure described in J Chem. Soc. (C) 1969, 183; 1.00 g, 4.17 mmol) in tetrahydrofuran, and the solution was heated at reflux for 2 h. After cooling, methanol (21 mL) was added, and volatile material was removed by distillation. The residue was taken up in 5% ethanolic sulfuric acid solution (12 mL) and heated at reflux for 2 h, then basified to pH 10 by addition of 2 M aq. sodium hydroxide solution and partitioned between water and ethyl acetate. The organic layer was dried (MgSO4) and evaporated. Chromatography (SiO2, heptane-ethyl acetate 2:1) yielded 8-bromo-2,3,4,5-tetrahydro-1H-benzo[b]azepine (865 mg, 92%). White solid, MS (ISP) m/e 226.1 (M+H).
	Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium acetate / ethanol; water / 0.75 h / 80 °C 2: methanesulfonic acid; phosphorus pentoxide / 20 h / 80 °C

Reference： [1]Wang, Chengpeng; Dong, Guangbin [Journal of the American Chemical Society, 2018, vol. 140, # 19, p. 6057 - 6061]
[2]Current Patent Assignee: ARBUTUS BIOPHARMA CORP - WO2021/158481, 2021, A1 Location in patent: Page/Page column 387-388
[3]Current Patent Assignee: XENON PHARMACEUTICALS INC - WO2008/46046, 2008, A1 Location in patent: Page/Page column 75
[4]Current Patent Assignee: ROCHE HOLDING AG - US2007/60567, 2007, A1 Location in patent: Page/Page column 32
[5]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/125444, 2014, A1

38
[ 123-75-1 ]
[ 32281-97-3 ]
[ 1034921-23-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium t-butanolate In toluene for 3h; Heating / reflux;	7.a a) 7-Pyrrolidin-1 -yl-3,4-dihydro-2H-naphthalen-1 -one; A dry flask is charged with 7-bromo-3,4-dihydro-2H-naphthalen-1-one (CASNo. 32281- 97-3, 0.102 g, 0.454 mmol), pyrrolidine (0.065 g, 0.909 mmol), 2-(di-f-butylphosphino)- biphenyl (0.020 g, 0.067 mmol), sodium tert-butoxide (0.087 g, 0.905 mmol) and toluene (3 ml_). The flask is evacuated and filled with nitrogen three times. Pd2(dba)3 (0.041 g, 0.045 mmol) is added and the mixture is heated to reflux for 3 hours, whereupon the mixture is cooled to room temperature, diluted with dichloromethane and washed with water. The organic phase is dried over sodium sulfate and concentrated. The resulting residue is purified by silica gel chromatography (elution with hexanes-ethyl acetate mixtures) to give 7- pyrrolidin-1-yl-3,4-dihydro-2H-naphthalen-1-one; 1H NMR (400 MHz, CDCI3) δ ppm 1.99 - 2.03 (m, 4 H), 2.06 - 2.14 (m, 2 H), 2.60 - 2.65 (m, 2 H)1 2.87 (t, J=6.1 Hz, 2 H), 3.28 - 3.35 (m, 4 H), 6.75 (dd, J=8.3, 2.8 Hz, 1 H), 7.12 (d, J=8.3 Hz, 1 H)1 7.19 (d, J=2.8 Hz1 1 H).

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2008/76336, 2008, A2 Location in patent: Page/Page column 76

39
[ 32281-97-3 ]
7-bromo-1,2-naphthoquinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With selenium(IV) oxide In acetic acid at 60℃; for 15h;	5 Under inert atmosphere, to a solution of tetralone derivatives (1 mmol) in glacial acetic acid (2 mL), selenium dioxide (250 mg, 2.2 equiv.) was added. The reaction mixture was warmed 15 Hrs at 60°C. The reaction mixture was then cooled to room temperature and was concentrated to dryness. purification (eluent CycHex:EtOAc 70:30 - Rf: 0.3). The orange residue was taken in Et2O (5 mL), the resulting solid was filtered off, washed with Et2O (2x5 mL) and dried under reduced pressure at 50°C for 15 Hrs to give a yellowish solid (271 mg, 52 %). 1H-NMR (400 MHz, DMSO): 2.37 (s, 3H, CH3), 6.41 (d, j 1.3 Hz, 1H, Ar), 7.61 (td, j 7.6 Hz, j 1.1 Hz, 1H, Ar), 7.68 (d, j 7.6 Hz, 1H, Ar), 7.79 (td, j 7.6 Hz, j 1.3, 1H, Ar), 7.97 (dd, j 7.6 Hz, j 1.1 Hz, 1H, Ar). M/Z (M+H)+ = 173.Compound 5: 7-bromonaphthalene-1,2-dione [Show Image] Compound 5 was obtained according to the general procedure II from 7-bromo-α-tetralone, followed by chromatography purification (eluent CycHex:EtOAc 70:30 - Rf: 0.3). The deep brown residue was taken in Et2O (10 mL), the resulting solid was filtered off, washed with Et2O (5x2 mL) and dried under reduced pressure at 50°C for 15 Hrs to give a brown solid (284 mg, 47 %). 1H-NMR (400 MHz, DMSO): 6.43 (d, j 10.2 Hz, 1H, Ar), 7.55 (d, j 8.1 Hz, 1H, Ar), 7.64 (d, j 10.2 Hz, 1H, Ar), 7.95 (dd, j 8.1 Hz, j 2.0, 1H, Ar), 7.99 (d, j 2.0 Hz, 1H, Ar).

Reference： [1]Current Patent Assignee: FAUST PHARMACEUTICALS - EP1961738, 2008, A1 Location in patent: Page/Page column 9-10

40
[ 939-97-9 ]
[ 32281-97-3 ]
[ 123291-20-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium hydroxide In methanol at 20℃; for 48h;

Reference： [1]Xu, Wen-Zhi; Huang, Zhi-Tang; Zheng, Qi-Yu [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5606 - 5608]

41
[ 32281-97-3 ]
[ 104-87-0 ]
[ 1039020-08-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium hydroxide In methanol at 20℃; for 48h;
	With sodium hydroxide In ethanol; water at 0 - 20℃;

Reference： [1]Xu, Wen-Zhi; Huang, Zhi-Tang; Zheng, Qi-Yu [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5606 - 5608]
[2]Wang, Kun; Niu, Saisai; Guo, Xin; Tang, Weijun; Xue, Dong; Xiao, Jianliang; Sun, Huaming; Wang, Chao [Journal of Organic Chemistry, 2022, vol. 87, # 5, p. 3804 - 3809]

42
[ 32281-97-3 ]
[ 1122-91-4 ]
[ 1039020-10-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium hydroxide In methanol at 20℃; for 48h;

Reference： [1]Xu, Wen-Zhi; Huang, Zhi-Tang; Zheng, Qi-Yu [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5606 - 5608]

43
[ 32281-97-3 ]
[ 3218-36-8 ]
[ 1039020-19-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium hydroxide In methanol at 20℃; for 48h;

Reference： [1]Xu, Wen-Zhi; Huang, Zhi-Tang; Zheng, Qi-Yu [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5606 - 5608]

44
[ 32281-97-3 ]
[ 1576-35-8 ]
[ 909248-37-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With methanol for 0.25h; Heating / reflux; Stage #2: toluene-4-sulfonic acid hydrazide With toluene-4-sulfonic acid In methanol for 7h; Heating / reflux;	III 7-Bromo-1-tetralone p-toluensulfonhydrazone. Into a round bottom flask containing the appropriate tetralone (2.20 g, 9.78 mmol), 40 mL of anhydrous methanol were added and the solution was refluxed for about 15 minutes. To the warm ketone solution, p-toluenesulfonhydrazide (2.82 g, 14.7 mmol) and about 20 mg of TsOH were added. The reaction mixture was refluxed under nitrogen atmosphere for 7 h, at which point, the solid formed was filtered and recrystallized with MeOH. After drying the solid under reduced pressure, 3.44 g (8.75 mmol) of the product was obtained in a 90% yield. 1H NMR (360 MHz, methanol-d6, δ): 8.00 (d, J=2.1, Ar, 1H), 7.86 (d, J=8.3, Ar, 2H), 7.67 (br s, N, 1H), 7.35 (d, J=8.2, Ar, 2H), 7.31 (dd, J=8.2, 2.1 Ar, 1H), 6.98 (d, J=8.2, Ar, 1H), 2.66 (t, J=5.8, C2, 2H), 2.49 (t, J=6.6, C2, 2H), 2.40 (s, CH3, 3H), 1.83 (p, J=6.1, C2, 2H). 13C NMR (75 MHz, methanol-d6): δ 152.7, 145.0, 139.6, 136.9, 134.8, 132.8, 131.0, 130.3, 128.8, 128.4, 120.8, 29.6, 26.4, 22.2, 21.7. Dept 135 NMR (75 MHz, methanol-d6): δ 132.8 (H), 131.0 (H), 130.3 (H), 128.8 (H), 128.4 (H), 29.6 (H2), 26.4 (H2), 22.2 (H2), 21.7 (H3).

Reference： [1]Current Patent Assignee: BAYLOR UNIVERSITY - US2009/76076, 2009, A1 Location in patent: Page/Page column 22

45
[ 32281-97-3 ]
[ 79-19-6 ]
[ 1131455-73-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With methanol for 0.166667h; Heating / reflux; Stage #2: thiosemicarbazide With acetic acid In methanol; water for 18h; Heating / reflux;	III 7-Bromo-2-tetralone. Into a round bottom flask kept at 0° C., AlCl3 (3.93 g, 29.5 mmol) and 5 mL of CH2Cl2 were added. The reaction system was put under nitrogen and stirred for about 7 minutes before adding 20 mL of a CH2Cl2 solution of β-tetralone (2.16 g, 14.7 mmol). After the reaction mixture was stirred for almost 10 minutes, 10 mL of Br2 (2.58 g, 16.2 mmol) were added and, the reaction mixture was stirred at room temperature for an hour. At the end of this period of time, the reaction mixture was poured into 50 mL of ice-water and, the product was extracted 3 times from the aqueous phase with EtOAc. The resultant organic phase was washed once with brine and dried under Na2SO4. After the crude reaction mixture was purified by flash chromatography (5% EtOAc/95% hex), 2.364 g (10.5 mmol) of monobromide was obtained in a 71% yield.1H NMR (300 MHz, CDCl3, δ): 7.33 (dd, J=8.1, 2.0, ArH, 1H), 7.27 (d, J=2.0, ArH, 1H), 7.10 (d, J=8.0, ArH, 1H), 3.55 (s, CH2, 2H), 3.02 (t, J=6.6, CH2, 2H), 2.53 (t, J=6.7, 6.4, CH2, 2H).13C NMR (75 MHz, CDCl3): δ 209.2, 135.6, 135.5, 130.9, 129.8, 129.2, 120.4, 44.5, 37.8, 27.8.Dept 135 NMR (75 MHz, CDCl3): δ 131.0 (CH), 129.9 (CH), 129.3 (CH), 44.6 (CH2), 37.9 (CH2), 27.9 (CH2).

Reference： [1]Current Patent Assignee: BAYLOR UNIVERSITY - US2009/76076, 2009, A1 Location in patent: Page/Page column 20

46
[ 32281-97-3 ]
[ 107-02-8 ]
[ 909248-39-1 ]

Yield	Reaction Conditions	Operation in experiment
11%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In hex at -50 - 20℃; for 1.33333h; Stage #2: acrolein In hex at 0℃; for 3h;	III 1-(7-Bromo-3,4-dihydronaphthalen-1-yl)-2-propen-1-ol. Into a dry round bottom flask containing the appropriate hydrazone (3.44 g, 8.76 mmol), 30 mL of TMEDA were added and, nitrogen was circulated through the reaction system. After the solution was cooled at -50° C., 14 mL of BuLi (2.5 M/hex, 35 mmol) were added and, the reaction mixture was stirred first at -50° C. for 40 minutes and then at room temperature for another 40 minutes. After bubbling stopped, the flask was cooled at 0° C. and, 2.4 mL of acrolein (1.96 g, 34.9 mmol) were added. The reaction was stirred at 0° C. for 3 h, at which point, 30 mL of ice water were added. The product was extracted once from the aqueous phase with EtOAc and, the combined organic phase was washed 3 times with H2O and with brine. The organic phase was dried under Na2SO4 and, the solvent was removed under vacuum. After the product was purified by flash chromatography (10% EtOAc/90% hex), 0.246 g (0.928 mmol) was obtained in an 11% yield. 1H NMR (300 MHz, CDCl3, δ): 7.60 (d, J=2.0, Ar, 1H), 7.26 (dd, J=8.0, 2.0, Ar, 1H), 7.00 (d, J=8.0, Ar, 1H), 6.22 (td, J=4.6, 0.7, C=C, 1H), 6.05 (ddd, J=17.3, 10.5, 5.4, C=CH2, 1H), 5.40 (dt, J=17.3, 1.5, C=C2, 1H), 5.25 (dt, J=10.4, 1.4, C=C2, 1H), 5.10 (dd, J=5.3, 1.0, COH, 1H), 2.67 (t, J=8.0, C2, 2H), 2.30 (m, C2, 2H), 1.92 (br s, H, 1H). Dept 135 NMR (75 MHz, CDCl3): δ 138.9 (H), 129.6 (H), 129.2 (H), 128.2 (H), 126.7 (H), 116.1 (H2), 72.6 (HOH), 27.5 (H2), 22.8 (H2).

Reference： [1]Current Patent Assignee: BAYLOR UNIVERSITY - US2009/76076, 2009, A1 Location in patent: Page/Page column 22

47
[ 32281-97-3 ]
[ 74-88-4 ]
[ 32281-99-5 ]

Yield	Reaction Conditions	Operation in experiment
44%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; for 2h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at -40 - 20℃; Inert atmosphere;
40%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 18h; Stage #3: With water; ammonium chloride In tetrahydrofuran	56.a a) 7-Bromo-2-methyl-3 ,4-dihydro-2H-naphthalen- 1 -oneTo a solution of LDA (2Af, 2.2 mL) in anhydrous THF (16 mL) at -780C 7-bromo-3,4- dihydro-l(2H)-naphthalenone (l.Og, 4.44 mmol) in THF (5 mL) was added dropwise and the mixture was stirred at - 780C for 30 minutes. Iodomethane (276 μL, 4.44 mL) was added and the reaction mixture left stirring for 18 hours at ambient temperature. Saturated ammonium chloride was added and then diethyl ether. The organic layer was washed with brine followed by drying and evaporation of solvent. The crude product was purified by column chromatography (6/1 petroleum ether-ethyl acetate) to obtain the mono- (424 mg, 40%) and di-methylated (112 mg, 10%) products.
17%	Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran at -78 - 0℃; for 0.666667h; Stage #2: 7-bromo-3,4-dihydro-2H-naphthalen-1-one In tetrahydrofuran at -78℃; for 1h; Stage #3: methyl iodide In tetrahydrofuran at 20℃;	21.A Butyllithium (5.60 mL, 14.0 mmol) was added to a solution of diisopropylamine (2.07 mL, 14.7 mmol) in THF (30 mL, 13.3 mmol) at -78°C under N2. This was stirred for 30 minutes and then at 0°C for 10 minutes. 7-Bromo-3,4-dihydronaphthalen- l(2H)-one (3.0 g, 13.3 mmol) was then added and stirred for 1 hour at -78°C. Iodomethane (1.08 mL, 17.3 mmol) was slowly added, and the reaction mixture was allowed to come to room temperature overnight. TLC ("thin layer chromatography") showed both mono and di addition. The reaction was then partitioned between EtOAc and water. The aqueous layer was washed with EtOAc twice, and the combined organics were washed with brine and then dried with Na2S04. The mixture was then concentrated down and purified on a column using EtOAc.hexane to give the 7-bromo-2-methyl-3,4-dihydronaphthalen-l(2H)-one (0.56 g, 2.36 mmol, 17%) as an oil.

Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 10h; Inert atmosphere;

Reference： [1]Takeda, Tadahiro; Terada, Masahiro [Journal of the American Chemical Society, 2013, vol. 135, # 41, p. 15306 - 15309]
[2]Current Patent Assignee: THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH - WO2009/39553, 2009, A1 Location in patent: Page/Page column 102-103
[3]Current Patent Assignee: ROCHE HOLDING AG - WO2011/123674, 2011, A1 Location in patent: Page/Page column 73-74
[4]Sleebs, Brad E.; Kersten, Wilhemus J. A.; Kulasegaram, Sanji; Nikolakopoulos, George; Hatzis, Effie; Moss, Rebecca M.; Parisot, John P.; Yang, Hong; Czabotar, Peter E.; Fairlie, W. Douglas; Lee, Erinna F.; Adams, Jerry M.; Chen, Lin; Van Delft, Mark F.; Lowes, Kym N.; Wei, Andrew; Huang, David C.S.; Colman, Peter M.; Street, Ian P.; Baell, Jonathan B.; Watson, Keith; Lessene, Guillaume [Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5514 - 5540]

48
[ 32281-97-3 ]
[ 73183-34-3 ]
[ 1135871-91-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In toluene at 90℃; for 12h; Inert atmosphere;
67%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In methanol at 65℃; for 14h; Inert atmosphere;
66%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In methanol at 60℃; for 10h; Inert atmosphere;

66%	With potassium acetate In methanol at 60℃; for 14h;	36.a ) Preparation of l-tetralone-7-boronic ester7-Bromo-tetralone (200mg, 0.89 mmol), bis(pinacolato)diboron (296mg, 1.16 mmol), Potassium acetate (192mg, 1.78 mmol) and [l,l'-bis(diphenylphosphino)ferrocene]- dichloropalladium (17mg, 0.023 mmol) were dissolved in 4 mL methanol and the solution was stirred at 6O0C for 14 hours. The reaction was allowed to cool, filtered over celite and concentrated to give a dark oil. The crude product was purified by flash chromatography on silica, using petroleum benzine and then 9:1 ratio of petroleum benzine and ethyl acetate as eluent to give the boronic ester (160mg, 66%). 1H NMR (d-chloroform) δ (ppm): 1.31 (s, 12H); 2.11 (m, 2H); 2.63 (t, 2H); 2.95 (t, 2H), 7.21 (s, IH), 7.85 (dd, IH), 8.47 (s, IH).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 100℃; for 1h; Inert atmosphere;	4.1 Step 1 : Preparation of 7-(4,4,5.5-tetramethyl-1,3.2-dioxaborolan-2-yl)tetralin-1 -one To a solution of 7-bromotetralin-1 -one (4.00 g, 17.8 mmol, 1 .00 equiv.) in dioxane (89.0 mL) was added potassium acetate (3.52 g, 35.5 mmol, 2.00 equiv.) and bis(pinacolato)diboron (5.01 g, 19.5 mmol, 1 .10 equiv.). The solution was degassed with argon for 5 min, then PdCl2(dppf) (0.68 g, 0.89 mmol, 0.05 equiv.) was introduced, and the reddish suspension was stirred at 100°C for 1 hour. The reaction mixture was diluted with EtOAc and water, and extracted with EtOAc. The total combined organic layer was washed with water and brine, dried with Na2SO 4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane:EtOAc) to give 7-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)tetralin-1 -one as a yellow gum. LC-MS (Method A), Rt = 1 .13 min, MS: (M+H) = 273 1H NMR (400 MHz, CDCl3) d ppm: 8.49-8.55 (m, 1 H), 7.90 (dd, 1 H), 7.28 (s, 1 H), 3.00 (t, 2H), 2.66-2.71 (m, 2H), 2.16 (quin, 2H), 1 .36 (s, 12H)

Reference： [1]Wang, Feng; Jeon, Kyu Ok; Salovich, James M.; Macdonald, Jonathan D.; Alvarado, Joseph; Gogliotti, Rocco D.; Phan, Jason; Olejniczak, Edward T.; Sun, Qi; Wang, Shidong; Camper, Demarco; Yuh, Joannes P.; Shaw, J. Grace; Sai, Jiqing; Rossanese, Olivia W.; Tansey, William P.; Stauffer, Shaun R.; Fesik, Stephen W. [Journal of Medicinal Chemistry, 2018, vol. 61, # 13, p. 5623 - 5642]
[2]Nguyen, William; Lee, Erinna F.; Evangelista, Marco; Lee, Mihwa; Harris, Tiffany J.; Colman, Peter M.; Smith, Nicholas A.; Williams, Luke B.; Jarman, Kate E.; Lowes, Kym N.; Haeberli, Cécile; Keiser, Jennifer; Smith, Brian J.; Fairlie, W. Douglas; Sleebs, Brad E. [ACS Infectious Diseases, 2021, vol. 7, # 5, p. 1143 - 1163]
[3]Sleebs, Brad E.; Kersten, Wilhemus J. A.; Kulasegaram, Sanji; Nikolakopoulos, George; Hatzis, Effie; Moss, Rebecca M.; Parisot, John P.; Yang, Hong; Czabotar, Peter E.; Fairlie, W. Douglas; Lee, Erinna F.; Adams, Jerry M.; Chen, Lin; Van Delft, Mark F.; Lowes, Kym N.; Wei, Andrew; Huang, David C.S.; Colman, Peter M.; Street, Ian P.; Baell, Jonathan B.; Watson, Keith; Lessene, Guillaume [Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5514 - 5540]
[4]Current Patent Assignee: THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH - WO2009/39553, 2009, A1 Location in patent: Page/Page column 83
[5]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD; Syngenta (in: Sinochem Holdings) - WO2021/9026, 2021, A1 Location in patent: Page/Page column 56

49
[ 6089-04-9 ]
[ 32281-97-3 ]
C₁₈H₂₁BrO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 3-(tetrahydropyran-2'-yloxy)propyne With n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Stage #2: 7-bromo-3,4-dihydro-2H-naphthalen-1-one In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;

Reference： [1]Hon, Yung-Son; Tseng, Tze-Wei; Cheng, Chia-Yi [Chemical Communications, 2009, # 37, p. 5618 - 5620]

50
[ 32281-97-3 ]
(+/-)-1-amino-7-bromo-1,2,3,4-tetrahydronaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With ammonium acetate; sodium cyanoborohydride In ethanol at 130℃; for 0.0333333h; Microwave irradiation;

Reference： [1]Location in patent: experimental part Dong, Li; Aleem, Saadat; Fink, Cynthia A. [Tetrahedron Letters, 2010, vol. 51, # 39, p. 5210 - 5212]

51
[ 32281-97-3 ]
[ 1187820-10-5 ]
[ 1187822-18-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In water; toluene; acetonitrile at 75℃; for 16h; Inert atmosphere;	4.4.3 4.3 7-[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-6-yl]-3,4-dihydro-2H-naphth-1-one 5 ml of acetonitrile, 5 ml of toluene and 6 ml of a 2M sodium carbonate solution are introduced into a round-bottomed flask and degassed under a stream of argon. 400 mg of 2-(4-chlorophenyl)imidazo[1,2-a]pyridine-6-boronic acid, 320 mg of 7-bromo-3,4-dihydro-2H-naphth-1-one and 75 mg of tetrakis(triphenylphosphine)palladium are added. The mixture is heated at 75° C. for 16 h and then allowed to return to ambient temperature. It is taken up between ethyl acetate and water. The organic phase is separated and dried. The solvent is concentrated under reduced pressure. The residue is purified by chromatography on silica gel, elution being carried out with a dichloromethane/acetone mixture. 238 mg of compound are obtained. 1H NMR spectrum (d6-DMSO, δ in ppm): 2.05 (m, 2H); 2.65 (m, 2H); 3.0 (m, 2H); 7.55 (m, 3H); from 7.6 to 7.75 (m, 2H); 7.95 (m, 1H); 8.05 (d, 2H); 8.2 (s, 1H); 8.45 (s, 1H); 9.0 (s, 1H). M+H=373.

Reference： [1]Current Patent Assignee: SANOFI - US2011/65699, 2011, A1 Location in patent: Page/Page column 10

52
potassium cyanide [ No CAS ]
[ 32281-97-3 ]
[ 506-87-6 ]
[ 1338093-88-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: potassium cyanide; 7-bromo-3,4-dihydro-2H-naphthalen-1-one; ammonium carbonate With sodium hydrogensulfite In ethanol at 130℃; for 24h; Stage #2: With hydrogenchloride In ethanol; water	23.A A 25 mL acid digestion Parr stainless steel bomb was charged with 7- bromo-3,4-dihydronaphthalen-l(2H)-one (1.50 g, 6.66 mmol), KCN (0.868 g, 13.3 mmol), ammonium carbonate (4.48 g, 46.6 mmol), and absolute EtOH (8 mL). The bomb was sealed, and the reaction mixture was heated in a 130°C oil bath for 24 hours. The reaction mixture was then cooled and rinsed into a flask with water, causing precipitation, and the mixture was slowly acidified to about pH 2 with 1M HCl (using caution as HCN was generated). The mixture was sparged with nitrogen for 30 minutes. Then the solids were isolated by vacuum filtration through qualitative filter paper on a Buchner funnel, rinsed with water, air dried, and dried in vacuo to give 7'-bromo-3',4'-dihydro-2'H-spiro[imidazolidine- 4,l'-naphthalene]-2,5-dione (1.82 g, 92% yield) as a powder.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2011/123674, 2011, A1 Location in patent: Page/Page column 75-76

53
[ 500-22-1 ]
[ 32281-97-3 ]
[ 1338094-00-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-pyridinecarboxaldehyde; 7-bromo-3,4-dihydro-2H-naphthalen-1-one With piperidine; acetic acid at 100℃; for 6h; Stage #2: With hydrogenchloride In water Stage #3: With sodium hydroxide In water	34.A Intermediate (E)-7-bromo-2-(pyridin-3-ylmethylene)-3,4- dihydronaphthalen-l(2H)-one was prepared according to the procedure described in EP0073663. A dry round bottomed flask with stir bar was charged with 7-bromo-3,4- dihydronaphthalen-l(2H)-one (5.7 g, 25 mmol), nicotinaldehyde (2.7 g, 25 mmol), acetic acid (2.5 mL) and piperidine (3 mL). The mixture was heated to 100°C for 6 hours. After cooling to room temperature, the mixture was concentrated in vacuo, using toluene to azeotrope residual volatiles (3 X 30 mL). The residue was suspended in aqueous IN HC1 (200 mL) and extracted with diethyl ether (50 mL). The organic phase was washed with aqueous 2N HC1 (100 mL). The aqueous phases were basified with NaOH pellets to pH 12, and the solid was filtered. The solid was washed with water (3 X 10 mL) and then dried solid by acetonitrile azeotrope on the rotovap (3 X 50 mL) to provide (E)-7-bromo-2-(pyridin-3- ylmethylene)-3,4-dihydronaphthalen-l(2H)-one (7.3 g, 89%).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2011/123674, 2011, A1 Location in patent: Page/Page column 84-85

54
[ 5414-19-7 ]
[ 32281-97-3 ]
[ 1338094-01-1 ]

Yield	Reaction Conditions	Operation in experiment
30.5%	With potassium <i>tert</i>-butylate In benzene for 3h; Reflux;	35.A 7-Bromo-3,4-dihydro-l(2H)-naphthalenone (4.0 g, 17.77 mmol) and 2-bromoethyl ether (2.90 mL, 23.1 mmol) were diluted with benzene (100 mL) followed by the addition of KOtBu (4.19 g, 37.3 mmol). The reaction was heated to reflux and stirred for 3 hours. The reaction was allowed to cool and diluted with ether and water. The layers were separated, and the organic layer was dried over MgS04, filtered and concentrated. The material was purified on silica gel eluting with 10-40% ethyl acetate/hexanes to yield 7- bromo-2',3,3',4,5',6'-hexahydro-lH-spiro[naphthalene-2,4'-pyran]-l-one (1.6 g, 5.421 mmol, 30.5% yield).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2011/123674, 2011, A1 Location in patent: Page/Page column 86-87

55
[ 32281-97-3 ]
[ 120801-75-4 ]
C₁₁H₉BrF₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; 1,3-bis(mesityl)imidazolium chloride In toluene at 100℃; for 1h;	4.2.1. Typical procedure for synthesizing aryl difluoromethyl ethers General procedure: To a toluene solution (0.4 mL) of IMes·HCl (2.7 mg, 0.0079 mmol), sodium carbonate (8.5 mg, 0.080 mmol), and 6,7-dimethyl-α-tetralone 1g (70 mg, 0.40 mmol) was added TFDA (100 μL, 0.48 mmol) at room temperature. The reaction mixture was stirred and heated at 80 °C for 1 h. After cooling the resulting mixture to room temperature, DDQ (182 mg, 0.80 mmol) and toluene (2 mL) was added and the mixture was heated at 100 °C for 2 h. Purification by column chromatography (SiO2, hexane) gave 6g (82 mg, 91% yield).
	With sodium carbonate; 1,3-bis(mesityl)imidazolium chloride In toluene at 100℃; for 1h;

Reference： [1]Location in patent: experimental part Fuchibe, Kohei; Koseki, Yuta; Aono, Tatsuya; Sasagawa, Hisashi; Ichikawa, Junji [Journal of Fluorine Chemistry, 2012, vol. 133, p. 52 - 60]
[2]Location in patent: experimental part Fuchibe, Kohei; Koseki, Yuta; Sasagawa, Hisashi; Ichikawa, Junji [Chemistry Letters, 2011, vol. 40, # 10, p. 1189 - 1191]

56
[ 32281-97-3 ]
[ 115269-99-3 ]
[ 1370549-45-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; palladium diacetate; potassium carbonate In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere; stereoselective reaction;	4.2.9. (E)-Di-tert-butyl-3-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)allyliminodicarbonate (3ia) General procedure: An oven-dried, two-necked round-bottom flask containing a stir bar was charged with an aryl bromide 1 (1.0 mmol), Pd(OAc)2 (6.8 mg, 0.03 mmol), K2CO3 (165.9 mg, 1.2 mmol), TEMPO (15.6 mg, 0.1 mmol), N,N-(Boc)2-allylamine (308.8 mg, 1.2 mmol) and DMF (3.0 ml) under nitrogen at room temperature. Following degassing three times, the flask was placed in an oil bath, and the mixture was stirred and heated at 100 °C. After an appropriate reaction time (Tables 2 and 3), the flask was removed from the oil bath and cooled to room temperature. Water (20 ml) was added, and the mixture was extracted with CH2Cl2 (3×20 ml). The combined organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The linear arylated allylamine was isolated out of the crude product by flash chromatography on silica gel using a mixture of ethyl acetate and hexane.
81%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutylammomium bromide; palladium diacetate; potassium carbonate In water at 90℃; for 3h; Inert atmosphere; regioselective reaction;

Reference： [1]Location in patent: experimental part Jiang, Zhen; Zhang, Lingjuan; Dong, Chaonan; Ma, Baode; Tang, Weijun; Xu, Lijin; Fan, Qinghua; Xiao, Jianliang [Tetrahedron, 2012, vol. 68, # 24, p. 4919 - 4926]
[2]Location in patent: experimental part Deng, Yuheng; Jiang, Zhen; Yao, Min; Xu, Dan; Zhang, Lingjuan; Li, Huanrong; Tang, Weijun; Xu, Lijin [Advanced Synthesis and Catalysis, 2012, vol. 354, # 5, p. 899 - 907]

57
[ 32281-97-3 ]
[ 6134-56-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylsilane; trifluoroacetic acid; at 20 - 50℃; for 4h;	(2) Synthesis of 6-bromo-1,2,3,4-tetrahydronaphthalene To 7.50 g of 7-bromo-3,4-dihydronaphthalen-1(2H)-one in trifluoroacetic acid (60 ml), 15.5 g of triethylsilane was added dropwise over 30 minutes at room temperature (the temperature of the reaction solution exothermically elevated from 27 C. to 50 C.). After the dropwise addition, the reaction solution was allowed to react at room temperature for 2 hours and then on a water bath at 50 C. for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was poured into 400 ml of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate (200 ml1, 100 ml1). The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane) to obtain 6.63 g of the desired product (yield 94%). Morphology: pale yellow oil

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 14187 - 14201
[2]Patent: US2012/209005,2012,A1 .Location in patent: Page/Page column 30
[3]Organic Letters,2018,vol. 20,p. 2042 - 2045
[4]Organic Letters,2019,vol. 21,p. 7179 - 7183

58
[ 32281-97-3 ]
[ 196929-78-9 ]
[ 1415108-20-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With titanium(IV) tetraethanolate In tetrahydrofuran at 66℃; for 10h; Inert atmosphere;	4.2.16. (R,E)-N-(7-Bromo-3,4-dihydronaphthalen-1(2H)-ylidene)-2-methylpropane-2-sulfinamide (13) A mixture of 5-bromo-1-tetralone 12 (1.5 g, 6.66 mmol), (R)-()-2-methyl-2 propanesulfinamide (1.21 g, 9.99 mmol) and titanium(IV) ethoxide (3.01 g, 13.32 mmol) were dissolved in anhydrousTHF (15 mL) and stirred at 66 °C for 10 h under argonatmosphere. The reaction mixture was cooled to 23 °C and ethylacetate and aq sodium bicarbonate was added. The mixture wasfiltered through a pad of celite and the aqueous layer was extractedwith ethyl acetate. The combined organic phase were dried overNa2SO4 and concentrated under reduced pressure. The crude residuewas purified by column chromatography over silica gel (5%EtOAc/hexanes) to afford 13 (1.9 g, 87%). Rf 0.5 (40% EtOAc/hexanes);1H NMR (400 MHz, CDCl3) δ 8.24 (d, J 2.2 Hz, 1H), 7.48 (dd,J 8.2, 2.2 Hz, 1H), 7.07 (d, J 8.2 Hz, 1H), 3.27 (ddd, J 17.6, 9.3,4.8 Hz, 1H), 3.05 (ddd, J 17.6, 7.5, 4.5 Hz, 1H), 2.81 (t, J 6.2 Hz,2H), 1.99e1.87 (m, 2H), 1.33 (d, J 2.3 Hz, 9H).
64%	With titanium(IV) tetraethanolate In tetrahydrofuran for 5h; Reflux;	Synthesis of the Intermediate Sulfinyl Imines A2General ProcedureTo a solution of the (R)-(+)-tert-butylsulfinamide (66 mmol) in tetrahydrofuran (350 ml) was added subsequently the ketone A1 (72.6 mmol) and titanium(IV)ethoxide (132 mmol) and the solution was stirred at reflux temperature for 5 h. The mixture was cooled to 22° C., treated with brine (400 ml), the suspension was stirred for 10 min and filtered over Dicalite. The layers were separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with water, dried and concentrated in vacuo. The residue was purified by chromatography on silica using cylohexane/ethyl acetate as the eluent to give the pure sulfinyl imine A2.Intermediate A2.1 (X≡-CR1a,R1b; R1a,R1b=H; W=-CR2a,R2b; R2a,R2b=H; p=1) Starting from 7-bromo-3,4-dihydro-2H-naphthalen-1-one {CAS[32281-97-3] (intermediate A1.1), the product (R)-2-methyl-propane-2-sulfinic acid [7-bromo-3,4-dihydro-2H-naphthalen-(1E)-ylidene]-amide (64% yield) was obtained as a yellow solid. MS (ISP): m/z=328.1 [M+H]+ and 329.9 [M+2+H]+.
64%	With titanium(IV) tetraethanolate In tetrahydrofuran Reflux;	General procedureTo a solution of the (R)-(+)-tert-butylsulfinamide (66 mmol) in tetrahydrofuran (350 ml) was added subsequently the ketone Al (72.6 mmol) and titanium(IV)ethoxide (132 mmol) and the solution was stirred at reflux temperature for 5 h. The mixture was cooled to 22 °C, treated with brine (400 ml), the suspension was stirred for 10 min and filtered over Dicalite. The layers were separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with water, dried and concentrated in vacuo. The residue was purified by chromatography on silica using cylohexane/ethyl acetate as the eluent to give the pure sulfinyl imine A2.Intermediate A2.1 (X = -CRla,Rlb; la, Rlb = H; W = -CR2a,R2h; R2*, R2b = H; p = 1)Starting from 7-bromo-3,4-dihydro-2H-naphthalen-l-one {CAS[32281-97-3] } (intermediate Al.l), the product (R)-2-methyl-propane-2-sulfinic acid [7-bromo-3,4-dihydro- 2H-naphthalen-(lE)-ylidene]-amide (64% yield) was obtained as a yellow solid. MS (ISP): m/z = 328.1 [M+H]+ and 329.9 [M+2+H]+.

Reference： [1]Ghosh, Arun K.; Jadhav, Ravindra D.; Simpson, Hannah; Kovela, Satish; Osswald, Heather; Agniswamy, Johnson; Wang, Yuan-Fang; Hattori, Shin-ichiro; Weber, Irene T.; Mitsuya, Hiroaki [European Journal of Medicinal Chemistry, 2018, vol. 160, p. 171 - 182]
[2]Current Patent Assignee: ROCHE HOLDING AG - US2012/302549, 2012, A1 Location in patent: Page/Page column 29
[3]Current Patent Assignee: ROCHE HOLDING AG - WO2012/163790, 2012, A1 Location in patent: Page/Page column 51

59
[ 50-00-0 ]
[ 32281-97-3 ]
7-bromo-2-methylene-3,4-dihydro-2H-naphthalen-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With magnesium sulfate; trifluoroacetic acid; diisopropylamine 2,2,2-trifluoroacetic acid salt In tetrahydrofuran at 60℃; for 24h;
40%	With N-methylanilinium trifluoroacetate In tetrahydrofuran for 6h; Reflux;	C1 Step CI . 7-Bromo-2-methylene-3,4-dihydronaphthalen-l(2H)-oneA solution of 7-bromo-3,4-dihydronaphthalen-l(2H)-one (2.00 g, 8.89 mmol) in THF (50 mL) was added to a mixture of N-methylanilinium trifluoroacetate (2.95 g, 13.3 mmol) and paraformaldehyde (1.20 g, 40.0 mmol) at rt. The resulting mixture was heated at reflux for 6 hours. The oil bath was removed and the mixture was allowed to cool to rt. Diethyl ether was added to the reaction mixture, which induced the separation of a red gum. The ethereal solution was decanted from the red gum into a separatory funnel and washed with half-saturated sodium bicarbonate solution. The red gum was triturated with diethyl ether, and the resulting ethereal solution was then used to extract the washing water. The combined organic layers were dried over magnesium sulfate. Filtration and concentration of the organic layer afforded a heavy red oil. The oil was purified using silica gel column chromatography (20: 1 hexanes/EtOAc) to afford 7-bromo-2-methylene- 3,4-dihydronaphthalen-l(2H)-one (0.850 g, 3.59 mmol, 40 % yield) as a thick viscous yellow oil. XH NMR (400MHz, chloroform-if) δ 8.23 (d, J=2.0 Hz, 1H), 7.60 (dd, J=8.2, 2.1 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 6.26 (q, J=1.3 Hz, 1H), 5.50 (q, J=1.7 Hz, 1H), 3.01 - 2.91 (m, 2H), 2.91 - 2.82 (m, 2H).

Reference： [1]Li, Yi-Pan; Zhu, Shou-Fei; Zhou, Qi-Lin [Organic Letters, 2019, vol. 21, # 23, p. 9391 - 9395]
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2012/162330, 2012, A1 Location in patent: Page/Page column 30

60
[ 201230-82-2 ]
[ 32281-97-3 ]
[ 1422386-12-6 ]
[ 1422386-54-6 ]

Yield	Reaction Conditions	Operation in experiment
66%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; triethylamine In 1,4-dioxane at 80℃; for 2h;

Reference： [1]Borhade, Sanjay R.; Sandström, Anja; Arvidsson, Per I. [Organic Letters, 2013, vol. 15, # 5, p. 1056 - 1059]

61
[ 542-69-8 ]
[ 32281-97-3 ]
7-methoxy-1-indanone [ No CAS ]
C₂₉H₃₀BrNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.5%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one; 7-methoxy-1-indanone With potassium <i>tert</i>-butylate In tetrahydrofuran for 12h; Stage #2: With ammonium acetate In tetrahydrofuran for 2h; Reflux; Inert atmosphere; Stage #3: 1-iodo-butane Further stages;	22 Example 22 - Preparation of Precursor 267 Example 22 - Preparation of Precursor 267 Precursor 253 Precursor 247 Precursor 267 To a dry, nitrogen-flushed flask was charged with Precursor 253 (1.97 g, 9.0 mmol), Precursor 247 (2.04 g, 9.0 mmol), potassium teri-butoxide (1.22 g, 10.9 mmol), anhydrous THF (40 mL). The mixture was stirred for 12 h. Excess ammonium acetate, acidic acid was added. The mixture was refluxed for 2 h. After cooling to room temperature, the crude mixture of the first intermediate was extracted with ethyl acetate and purified by chromatography on silica gel with mixture of hexane and ethyl acetate (v/v = 10: 1). To a dry, nitrogen- flushed flask was charged the first intermediate (0.53 g, 1.4 mmol), potassium teri-butoxide (0.35 g, 3.1 mmol), 1-iodobutane (0.35 mL, 3.1 mmol), and anhydrous THF (20 mL). The mixture was stirred for 24 h. The crude mixture of the second intermediate was extracted with ethyl acetate and purified by chromatography on silica gel with mixture of hexane and ethyl acetate (v/v = 10: 1). To a dry, nitrogen- flushed flask was charged with the second intermediate (0.64 g, 1.3 mmol), 4,5-dichloro-3,6-dioxocyclohexa-l,4-diene-l,2-dicarbonitrile(DDQ) (0.42 g, 1.8 mmol), and anhydrous 1,4-dioxane (40 mL). The mixture was refluxed for 24 h. After cooling to room temperature, ethyl acetate was added, and the mixture was stirred for five minutes. The crude mixture was extracted with saturated sodium dicarbonate solution, dichloromethane and purified by chromatography on silica gel with mixture of hexane and ethyl acetate (v/v = 10: 1). 0.61 g of yellow solid was obtained. Yield: 79.5%. H NMR (CDC13, 400 MHz): δ 9.62 (s, 1H), 8.00 (s, 1H), 7.77-7.75 (m, 4H), 7.48 (t, J = 7.9 Hz, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 4.23 (s, 3H), 2.17-2.00 (m, 4H), 1.08-1.03 (m, 4H), 0.67-0.57 (m, 10H).

Reference： [1]Current Patent Assignee: GANGDA KEQIAO; THE UNIVERSITY OF HONG KONG - WO2013/152727, 2013, A1 Location in patent: Page/Page column 34; 35

62
[ 75693-15-1 ]
[ 32281-97-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With acetic acid; 1,1'-(phenyl-l3-iodanediyl)bis(pyridinium)trifluoromethanesulfonate In 1,2-dichloro-ethane at 60℃; for 1.5h; Inert atmosphere; Molecular sieve; chemoselective reaction;
90%	With pivalaldehyde In toluene at 40℃; for 0.5h; Flow reactor;

Reference： [1]Mikhael, Myriam; Adler, Sophia A.; Wengryniuk, Sarah E. [Organic Letters, 2019, vol. 21, # 15, p. 5889 - 5893]
[2]Chorghade, Rajeev; Battilocchio, Claudio; Hawkins, Joel M.; Ley, Steven V. [Organic Letters, 2013, vol. 15, # 22, p. 5698 - 5701]

63
[ 32281-97-3 ]
[ 25059-70-5 ]
[ 1368898-69-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With sodium hydride; sodium iodide In mineral oil; <i>tert</i>-butyl alcohol at 20 - 25℃; for 0.333333h; Stage #2: 2-chloroethyl dimethyl sulfonium iodide In mineral oil; <i>tert</i>-butyl alcohol	6 7'-Bromo-3',4'-dihydro-l'H-spiro[cyclopropane-l,2'-naphthalene]-l'-one To a solution of 7-bromo-l-tetralone (1.03 g, 4.58 mmol) in tert-butanol (10 mL) was added sodium iodide (0.131 g, 0.872 mmol) and sodium hydride (0.349 g, 60% suspension in mineral oil, 8.72 mmol). The reaction mixture was stirred at r.t. for 20 min. Then (2- chloroethyl)dimethylsulfonium iodide (Intermediate 5, 1.10 g, 4.36 mmol) was added portionwise over 1 h. After the reaction had reached completion, water (15 mL) was added and the resulting mixture was extracted with EtOAc (3 x 15 mL). The combined organic layers were dried with sodium sulfate, filtered and concentrated in vacuo. The product was purified by flash chromatography using 5% EtOAc in heptanes as eluent to give the title compound (0.789 g, 78%). 1H MR (400 MHz, CDC13) δ ppm 0.84 (dd, 2 H), 1.40 (dd, 2 H), 1.95 (t, 2 H), 2.93 (t, 2 H), 7.14 (d, 1 H), 7.55 (dd, 1 H), 8.11 (d, 1 H); MS (ES+) m/z 250.98, 253.03 [M+H]+.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2013/190300, 2013, A1 Location in patent: Page/Page column 29

64
[ 32281-97-3 ]
[ 292638-85-8 ]
[ 1521283-97-5 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one; acrylic acid methyl ester With potassium <i>tert</i>-butylate In tetrahydrofuran at 25℃; Cooling with ice; Stage #2: With potassium hydroxide In tetrahydrofuran; water at 75℃; for 1.5h;	7 7'-Bromo-3',4'-dihydro-l'H-spiro[cyclohexane-l,2'-naphthalene]-l',4-dione 7-Bromo-3,4-dihydronaphthalen-l(2H)-one (10.3 g, 45.8 mmol) and methyl acrylate (9.08 mL, 101 mmol) was dissolved in THF (55 mL) and cooled in an ice bath. Potassium tert-butoxide (6.16 g, 54.9 mmol) was added in portions. The mixture was stirred for 1.5 h at r.t. Water (80 mL) and potassium hydroxide (2.57 g, 45.8 mmol) were added and the mixture was heated to 75 °C overnight in an open system. The mixture was cooled to r.t. and filtered. The obtained solid was dried in vacuo yielding the title compound (11.5 g, 82% yield): 1H MR (CDC13) δ ppm 1.74 - 1.87 (m, 2 H), 2.15 (t, 2 H), 2.24 - 2.43 (m, 4 H), 2.62 - 2.72 (m, 2 H), 3.00 (t, 2 H), 7.16 (d, 1 H), 7.61 (dd, 1 H), 8.16 (d, 1 H); MS (ES+) m/z 307, 309 [M+H]+.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2013/190300, 2013, A1 Location in patent: Page/Page column 29

65
[ 75-15-0 ]
[ 32281-97-3 ]
[ 74-88-4 ]
2-(bismethylsulfanylmethylene)-7-bromo-3,4-dihydro-2H-naphthalen-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: carbon disulfide; 7-bromo-3,4-dihydro-2H-naphthalen-1-one With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide; benzene at 0 - 20℃; for 4h; Stage #2: methyl iodide In N,N-dimethyl-formamide; benzene at 20℃;	1.1 Step 1 Example 1 7-(4-Cyclobutyl-thiazol-2-yl)-5,6-dihydro-naphthalene-2-carboxylic acid Step 1 To an ice cold solution of potassium tert-butoxide (26.7 g, 0.24 mol) in benzene (170 ml) and DMF (50 ml) was added via dropping funnel a solution of 7-bromo-l-tetralone (22.5 g, 0.10 mol) and carbon disulfide (7.6 g, 0.10 mol) in benzene (50 ml). The rate of addition was controlled to maintain an internal temperature below 20°C. After the addition was complete, the reaction was warmed to room temperature and stirred for 4 h. Methyl iodide (30 g, 0.21 mol) was added dropwise and the mixture was stirred at room temperature overnight then carefully quenched with ice cold water (400 ml). The layers were separated and the organic phase was washed with water (2 x 100 ml). The aqueous washings were back-extracted with diethyl ether (2 x 100 ml). The combined organic layers were dried over MgS04 and concentrated. The residue was treated with 2 volumes of diethyl ether and stored in a refrigerator overnight. Collected 26.1 g (79%) of 2-(bis-methylsulfanyl-methylene)-7-bromo-3,4-dihydro-2H- naphthalen-l-one via filtration as two crops of crystals. Mp = 88°C.
60.15%	Stage #1: carbon disulfide; 7-bromo-3,4-dihydro-2H-naphthalen-1-one With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide; toluene at 0 - 20℃; for 4h; Stage #2: methyl iodide In N,N-dimethyl-formamide; toluene at 20℃; for 18h;	17.1 Step 1: Synthesis of Compound WX133-2 At 0° C., to a solution of potassium tert-butoxide (5.98 g, 53.30 mmol) in DMF (13.00 mL) and toluene (37.00 mL) was added a solution of WX133-1 (5.00 g, 22.21 mmol) and carbon disulfide (1.69 g, 22.21 mmol, 1.34 mL) in toluene (10.00 mL) dropwise. The system was stirred at room temperature for 4 hours, and then methyl iodide (6.62 g, 46.64 mmol, 2.90 mL) was added, and the reaction mixture was stirred at room temperature for 18 hours. After the reaction was complete, 100 mL water was added. The mixture was extracted with methyl tert-butyl ether (100 mL×3). The organic phases were combined, and washed with brine (25 mL×2). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to afford Compound WX133-2 (4.40 g, 60.15% yield), yellow solid.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/86697, 2014, A1 Location in patent: Page/Page column 18
[2]Current Patent Assignee: PHAENO THERAPEUTICS - US2019/375744, 2019, A1 Location in patent: Paragraph 0215; 0216

66
[ 32281-97-3 ]
[ 1779-49-3 ]
[ 740842-57-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: 7-bromo-3,4-dihydro-2H-naphthalen-1-one In tetrahydrofuran at 20℃; Inert atmosphere;
52%	Stage #1: Methyltriphenylphosphonium bromide With n-butyllithium In tetrahydrofuran at -45℃; for 1h; Stage #2: 7-bromo-3,4-dihydro-2H-naphthalen-1-one In tetrahydrofuran at -45 - 20℃;

Reference： [1]Zhao, Zhensheng; To, Avery J.; Murphy, Graham K. [Chemical Communications, 2019, vol. 55, # 98, p. 14821 - 14824]
[2]Koehler, Michael F. T.; Bergeron, Philippe; Choo, Edna F.; Lau, Kevin; Ndubaku, Chudi; Dudley, Danette; Gibbons, Paul; Sleebs, Brad E.; Rye, Carl S.; Nikolakopoulos, George; Bui, Chinh; Kulasegaram, Sanji; Kersten, Wilhelmus J. A.; Smith, Brian J.; Czabotar, Peter E.; Colman, Peter M.; Huang, David C. S.; Baell, Jonathan B.; Watson, Keith G.; Hasvold, Lisa; Tao, Zhi-Fu; Wang, Le; Souers, Andrew J.; Elmore, Steven W.; Flygare, John A.; Fairbrother, Wayne J.; Lessene, Guillaume [ACS Medicinal Chemistry Letters, 2014, vol. 5, # 6, p. 662 - 667]

67
[ 407-47-6 ]
[ 32281-97-3 ]
C₁₅H₁₂BrF₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper(II) acetate monohydrate In tert-Amyl alcohol at 20 - 100℃; for 12.33h; Schlenk technique; Sealed tube; regioselective reaction;

Reference： [1]Kathiravan, Subban; Nicholls, Ian A. [European Journal of Organic Chemistry, 2014, vol. 2014, # 32, p. 7211 - 7219]

68
[ 32281-97-3 ]
[ 768-35-4 ]
7-(3-fluorophenyl)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; caesium carbonate In toluene at 80℃; Schlenk technique; Inert atmosphere; Sealed tube;	6.1 Step 1. 7-(3-Fluorophenyl)-3,4-dihydronaphthalen-1(2H)-one Step 1. 7-(3-Fluorophenyl)-3,4-dihydronaphthalen-1(2H)-one Cesium carbonate (869 mg, 2.67 mmol) was added to a solution of 7-bromo-3,4-dihydronaphthalen-1(2H)-one (300 mg, 1.33 mmol), (3-fluorophenyl) boronic acid (372 mg, 2.67 mmol) and toluene (20 mL) in a 50 mL Schlenk tube. A nitrogen atmosphere was established by evacuating and refilling with nitrogen (3*), then tetrakis(triphenylphosphine)palladium (0) (15 mg, 0.013 mmol) was added to the reaction. The flask was sealed and heated in a 80° C. oil bath overnight. The resulting mixture was cooled to room temperature. The reaction was then diluted with ethyl acetate and filtered through celite. Ethyl acetate (30 mL) was used to wash the flask and the combined organic filtrate was concentrated. The resulting crude residue was purified on a Teledyne-Isco Combiflash machine (40 g column, hexanes→100% ethyl acetate/hexanes, gradient), to afford 174 mg (54%) of 7-(3-fluorophenyl)-3,4-dihydronaphthalen-1(2H)-one.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2015/175567, 2015, A1 Location in patent: Paragraph 0127; 0128

69
[ 67-56-1 ]
[ 201230-82-2 ]
[ 32281-97-3 ]
[ 116047-26-8 ]

Yield	Reaction Conditions	Operation in experiment
	With palladium diacetate; triethylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In N,N-dimethyl-formamide; at 70℃; for 48h;	To a mixture of 7- bromo-3,4-dihydronaphthalen-l(2H)-one A19-l (15 g, 67 mmol) and Pd(OAc)2 (0.75 g, 3.4 mmol)DIVIF (2OmL) and MeOH (300 mL) were added Xant-Phos (3.9 mg, 4.7 mmol) and Et3N (34 g, 0.33 mmol). Then the mixture was heated to 70 C for 48 h under a CO atmosphere (55 psi). Aftercooling to room temperature, the reaction was filtered and the filtrate was concentrated in vacuo to afford a residue, which was partitioned between EA and water. The organic layer was separated andaqueous layer was extracted with EA twice. The combined organic layers were washed with water, dried and concentrated in vacuo to obtain a residue, which was purified by column chromatography over silica gel to afford A19-2. MS (ESI) m / e (M+H): 204.1/205.1.

Reference： [1]Patent: WO2015/176267,2015,A1 .Location in patent: Page/Page column 116

70
[ 32281-97-3 ]
[ 54881-49-1 ]
C₁₈H₁₄BrClO₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 3549 - 3561
[2]Chemical Biology and Drug Design,2016,vol. 88,p. 889 - 898

71
[ 5417-17-4 ]
[ 32281-97-3 ]
C₁₉H₁₆BrClO₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 3549 - 3561
[2]Chemical Biology and Drug Design,2016,vol. 88,p. 889 - 898

72
[ 62903-13-3 ]
[ 32281-97-3 ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 8757 - 8760

73
[ 90923-75-4 ]
[ 32281-97-3 ]
C₂₀H₁₆BrNO [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5703 - 5706

74
[ 21005-45-8 ]
[ 32281-97-3 ]
C₂₀H₁₆BrNO [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5703 - 5706

75
[ 32281-97-3 ]
[ 105-36-2 ]
ethyl 2-(7-bromo-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.7%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With lithium hexamethyldisilazane In tetrahydrofuran at -78 - 0℃; for 0.5h; Stage #2: ethyl bromoacetate In tetrahydrofuran at -78 - 20℃; for 19h;	19 Ethyl 2-(7-bromo-1 -oxo-1 ,2,3,4-tetrahyd ronaphthalen-2-yl)acetate LiHMDS (1 .0 M in THE) (11 .00 mL, 11 .00 mmol) was added to a solution of 7-bromo-3,4-dihydronaphthalen-1 (2H)-one (2.251 g, 10 mmol) in THE (10 mL) slowly (over 10 mm) at -78 00.The resulting reaction mixture was allowed to warm to 0 C and stirred at this temperature for 30mm, then cooled to -78 00 To this reaction mixture was added ethyl 2-bromoacetate (1 .391mL, 11 .00 mmol) in THE (2 mL) slowly at -78 00. The resulting mixture was stirred at -78 00 for1 h then warmed to ambient temperature and stirred for 18 h. The reaction mixture was quenched with 10 mL of saturated solution of NH4CI and diluted with H20 (10 mL). The mixture was extracted with EtOAc (3 x 30 mL). The combined organic layer was washed with brine (30 mL), dried over MgSO4, filtered, concentrated under reduced pressure, and purified via silica gelchromatography to afford the title compound (1.6881 g, 2.170 mmol, 21.70% yield) as a colorless oil. LC-MS m/z310.9 (M+H), 1.09 mm (ret. time).
21.7%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one; ethyl bromoacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78 - 0℃; for 0.666667h; Stage #2: In tetrahydrofuran at -78 - 20℃; for 19h;	19 Ethyl 2-(7-bromo-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)acetate LiHMDS (1.0 M in THF) (11.00 mL, 11.00 mmol) was added to a solution of 7-bromo-3,4- dihydronaphthalen-1(2H)-one (2.251 g, 10 mmol) in THF (10 mL) slowly (over 10 min) at -78 °C. The resulting reaction mixture was allowed to warm to 0°C and stirred at this temperature for 30 min, then cooled to -78 °C. To this reaction mixture was added ethyl 2-bromoacetate (1.391 mL, 11.00 mmol) in THF (2 mL) slowly at -78 °C. The resulting mixture was stirred at -78 °C for 1 h then warmed to ambient temperature and stirred for 18 h. The reaction mixture was quenched with 10 mL of saturated solution of NH4Cl and diluted with H2O (10 mL). The mixture was extracted with EtOAc (3 x 30 mL). The combined organic layer was washed with brine (30 mL), dried over MgSO4, filtered, concentrated under reduced pressure, and purified via silica gel chromatography to afford the title compound (1.6881 g, 2.170 mmol, 21.70 % yield) as a colorless oil. LC-MS m/z 310.9 (M+H)+, 1.09 min (ret. time).

Reference： [1]Current Patent Assignee: OTSUKA HOLDINGS CO LTD; GLAXOSMITHKLINE PLC - WO2016/203401, 2016, A1 Location in patent: Page/Page column 107; 108
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC; OTSUKA HOLDINGS CO LTD - WO2018/104766, 2018, A1 Location in patent: Page/Page column 108

76
[ 32281-97-3 ]
[ 616-38-6 ]
7-Brom-2-methoxycarbonyl-1-tetralon [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydride In methanol; toluene at 90℃; for 2h;	2.1 First step: methyl 7-bromo-1-oxo-tetralin-2-carboxylate (2A) Dissolve 7-bromo-3,4-dihydro-2H-1-naphthone (5g, 22.2mmol) in 15mL of toluene, add dimethyl carbonate (15mL) and 0.1mL of methanol, Sodium hydride (1.07g, 44.4mmol) was slowly added at room temperature. After the addition, the temperature was raised to 90 °C and stirred for 2h. After cooling to room temperature, adding 20 mL of saturated aqueous ammonium chloride to quench the reaction, adding 20 mL of ethyl acetate for extraction, the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the target compound methyl 7-bromo-1-oxo-tetralin-2-carboxylate (2A), brown solid (6.4 g, yield: 100%).
	With potassium <i>tert</i>-butylate; sodium hydride at 0℃; Inert atmosphere;
	With sodium hydride In mineral oil for 12h; Reflux;

Reference： [1]Current Patent Assignee: HAISCO PHARMACEUTICAL GROUP CO., LTD. - CN112778284, 2021, A Location in patent: Paragraph 0251-0258
[2]Qiu, Jia-Shen; Wang, Yao-Feng; Qi, Gui-Rong; Karmaker, Pran G.; Yin, Hong-Quan; Chen, Fu-Xue [Chemistry - A European Journal, 2017, vol. 23, # 8, p. 1775 - 1778]
[3]Ding, Tianqi; Jiang, Lvqi; Yang, Jie; Xu, Yimin; Wang, Guixiang; Yi, Wenbin [Organic Letters, 2019, vol. 21, # 15, p. 6025 - 6028]

77
[ 32281-97-3 ]
[ 123-11-5 ]
C₁₈H₁₅BrO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium hydroxide In methanol; water at 25℃; for 28h;

Reference： [1]Shibuya, Yoshiki; Itoh, Yoshimitsu; Aida, Takuzo [Chemistry - An Asian Journal, 2017, vol. 12, # 7, p. 811 - 815]

78
[ 32281-97-3 ]
(E)-7-bromo-3,4-dihydronaphthalene-1(2H)-oneoxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydroxylamine hydrochloride; sodium acetate In ethanol for 2h; Reflux;	5.1 Step 1: (E) -7- bromo-3,4-dihydro-naphthalene -1 (2H) - one oxime 7-bromo-3,4-dihydro -2H-1- tetralone (3.0g, 13.3mmol) added to the reaction flask, hydroxylamine hydrochloride (1.1g, 16mmol), sodium acetate (1.31g, 16mmol) and ethanol ( 60mL), the reaction mixture was refluxed for 2 hours.Completion of the reaction, the solvent was concentrated under reduced pressure, water was added (20mL) and ethyl acetate (60 mL), separated, the organic phase was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate.The solvent was evaporated under reduced pressure to give the title compound as an off-white solid (3.0g, 95%)

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - CN106916091, 2017, A Location in patent: Paragraph 0262; 0265; 0266

79
[ 32281-97-3 ]
[ 100-52-7 ]
[ 17356-08-0 ]
9-bromo-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With trimethylsilyl bromide; iron(III) chloride hexahydrate In acetonitrile at 90℃; for 2h; Microwave irradiation; Sealed tube; Inert atmosphere;	3.2. General Procedure for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-thiones (4) General procedure: A high-pressure microwave vessel (capacity 10 mL) was loaded with ketones (0.5 mmol),benzaldehydes (0.5 mmol), thiourea (0.75 mmol), FeCl36H2O (0.05 mmol) and TMSBr (0.5 mmol) inCH3CN (3.0 mL). The vessel was degassed, refilled with nitrogen, and sealed. Then the mixture was heated to 90 °C for 2 h under microwave irradiation using a CEM Discover (fixed power, 30 W). After cooling, the solids which had precipitated out were separated by filtration, and the solids obtained were washed with CH3CN to give the desired products 4.

Reference： [1]Zhao, Fei; Jia, Xiuwen; Li, Pinyi; Zhao, Jingwei; Huang, Jun; Li, Honglian; Li, Lin [Molecules, 2017, vol. 22, # 9]

80
[ 32281-97-3 ]
[ 100-52-7 ]
[ 57-13-6 ]
9-bromo-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With trimethylsilyl bromide; iron(III) chloride hexahydrate In acetonitrile at 90℃; for 2h; Microwave irradiation; Sealed tube; Inert atmosphere;	3.3. General Procedure for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones (6) General procedure: A high-pressure microwave vessel (capacity 10 mL) was loaded with ketones (0.5 mmol),benzaldehydes (0.5 mmol), urea (0.75 mmol), FeCl36H2O (0.05 mmol) and TMSBr (0.5 mmol) in CH3CN (3.0 mL). The vessel was degassed, refilled with nitrogen, and sealed. Then the mixture was heated to 90 °C for 2 h under microwave irradiation using a CEM Discover (fixed power, 30 W). Aftercooling, the solids which had precipitated out were separated by filtration, and the solids obtained were washed with CH3CN to give the desired products 6.

Reference： [1]Zhao, Fei; Jia, Xiuwen; Li, Pinyi; Zhao, Jingwei; Huang, Jun; Li, Honglian; Li, Lin [Molecules, 2017, vol. 22, # 9]

81
[ 32281-97-3 ]
[ 593-51-1 ]
7-bromo-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With titanium(IV) isopropylate; triethylamine In ethanol at 20℃; for 22h; Sealed tube;	7-Bromo-N-methyl- 1,2,3,4-tetrahydronaphthalen-1-amine (MDW-2- 124) In a modification of a literature procedure, 7-bromotetralone (1.50 g, 6.68 mmol) was dissolved in EtOH (13.5 mL) in a resealable tube, whereupon Ti(OiPr)4 (4.7 g, 4.9 mL, 17 mmol), Et3N (3.4 g, 4.7 mL, 34 mmol) and MeNH3C1 (2.26 g, 33.5 mmol) were sequentially added.2 The tube was sealed, and the reaction was stirred at room temperature for 22 h. The solution was cooled to 0°C, and NaBH4 (0.506 g, 13.4 mmol) was added in one portion. Stirring was continued at 0 °C for 1 h, and the mixture was added to 2 M aq. NH4OH (20 mL). The suspension was filtered through a pad of Celite, and the filter cake was washed with hot EtOAc (250 mL). The filtrate was concentrated under reduced pressure and partitioned between CH2C12 (25 mL) and saturated aq. NaHCO3 (15 mL). The organic layer was separated and extracted with 1 M HC1 (3 x 20 mL).The combined aqueous extracts were made basic with 6 M NaOH and extracted with CH2C12 (3 x50 mL). The combined organic extracts were dried (Na2504) and concentrated under reducedpressure. The cmde residue was purified via flash chromatography (5i02) eluting withCH2C12/MeOH/Et3N (98:1:1) affording 1.27 g (79%) of MDW-2- 124 as a pale yellow oil. ‘HNMR (400 MI-Tz, CDC13) ö 7.50 (d, J= 2.1 Hz, 1H), 7.23 (dd, J= 8.2, 2.2 Hz, 1H), 6.93 (d, J8.2 Hz, 1H), 3.60 (t, J= 4.9 Hz, 1H), 2.78 -2.59 (comp, 2H), 2.48 (s, 3H), 1.96- 1.66 (comp,4H)

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - WO2017/190107, 2017, A1 Location in patent: Page/Page column 83

82
[ 32281-97-3 ]
[ 501-53-1 ]
benzyl (7-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With ammonium acetate; sodium cyanoborohydride In methanol at 60℃; for 25h; Stage #2: benzyl chloroformate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 16h;	Benzyl (7-bromo- 1,2,3,4-tetrahydronaphthalen-1-yl)carbamate (MDW-1-193) A solution containing 7-bromotetralone (0.500 g, 2.22 mmol), NH4OAc (1.71 g, 22.2 mmol), and NaBH3CN (691 mg, 11.1 mmol) in MeOH (11 mL) was stirred at 60 °C for 25 h. The reaction mixture was concentrated under reduced pressure and partitioned between CH2C12 (25 mL) and saturated aq. NaHCO3 (25 mL). After the organic layer was separated, the aqueous layer wasdiluted with 6 M NaOH (5 mL) and extracted with CH2C12 (3 x 25 mL). The combined organic extracts were dried (Na2SO4), and concentrated under reduced pressure. The crude residue was taken up in CH2C12 (22 mL) and cooled to 0 °C, followed by sequential addition of DIPEA (0.55 g, 0.75 mL, 4.3 mmol) and CbzCl (0.44 g, 0.37 mL, 2.6 mmol). The solution was stirred for 16 h, allowing to warm to room temperature. The reaction mixture was diluted with CH2C12 (20 mL),washed with 1 N HC1 (2 x 25 mL), 1 N NaOH (2 x 25 mL), brine (1 x 25 mL), dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified via flash chromatography (Si02) eluting with hexanes/EtOAc (9:1) to give 0.502 g (63%) of MDW-1-193 as a white solid. ‘H NMR (400 MHz, CDC13): ö 7.48 (brs, J= 2.1 Hz, 1 H), 7.41 -7.28 (comp, 5 H), 7.25 (dd, J= 8.4, 2.1 Hz, 1 H), 6.92 (d, J= 8.2 Hz, 1 H), 5.40 (d, J= 9.0 Hz, 1 H), 5.11 (s, 2H), 4.89- 4.79 (m, 1 H), 2.76- 2.60 (comp, 2 H), 2.07 - 1.95 (m, 1 H), 1.89- 1.68 (comp, 3 H). HRMS (ESI) m/z calcd for C18H18BrNO2 (M+Na), 382.0413; found 382.0417

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - WO2017/190107, 2017, A1 Location in patent: Page/Page column 84

83
[ 110-85-0 ]
[ 32281-97-3 ]
7-(piperazin-1-yl)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; ruphos In <i>tert</i>-butyl alcohol at 45 - 100℃; for 3.75h; Sealed tube;	7-(piperazin- 1-yl)-3,4-dihydronaphthalen- 1(211)-one (MDW-1-262) A resealable tube was charged with 7-bromo-1-tetralone (0.500 g, 2.22 mmol), piperazine (1.913 g, 22.2 mmol), C52CO3 (1.086 g, 3.33 mmol) and degassed tBuOH (11.1 mL). The suspension was stirred at 45°C for 15 mm, whereupon a freshly prepared tBuOH solution (0.67 mL) containing Pd2dba3 (40.6 mg, 0.044 mmol) and RuPhos (41.5 mg, 0.088 mmol) that had been stirred at 60 °C for 30mm was added. The tube was sealed, and the reaction was stirred at 100 °C for 3 h. After cooling to room temperature, the mixture was filtered through Celite, the filter cake was washed with CH2C12 (200 mL), and the filtrate was concentrated. The residue was dissolved in CH2C12 (50 mL), washed with saturated aq. NaHCO3 (2 x 50 mL), and extracted with 1 N HC1 (4 x 30 mL). The combined acidic aqueous extracts were made basic and extracted with CH2C12 (4 x 50 mL),after which the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. The cmde material was purified via flash chromatography (Si02) eluting with CH2C12/MeOH/Et3N (97:2:1) affording 0.418 g (82%) of MDW-1-262 as a red oil. ‘H NMR (400 MHz, CDC13) ö 7.46 (d, J= 2.8 Hz, 1 H), 7.08 (d, J= 8.4 Hz, 1 H), 7.02 (dd, J 8.4, 2.8 Hz, 1 H), 3.14- 3.06 (comp, 4 H), 3.00 -2.93 (comp, 4 H), 2.79 (t, J= 6.1 Hz, 2 H), 2.70 (br s,1 H), 2.54 (m, 2 H), 2.01 (m, 2 H). HRMS (ESI) m/z calcd for C14H18N20 (M+H), 231.1492; found 231.1497
82%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; ruphos In <i>tert</i>-butyl alcohol at 60 - 100℃; for 3.5h; Sealed tube;	7-(Piperazin-l-yl)-3,4-dihydronaphthalen-l(2/?)-one (2). A resealable tube was charged with tetralone 1 (0.500 g, 2.22 mmol), piperazine (1.913 g, 22.2 mmol), CS2CO3 (1.086 g, 3.33 mmol) and degassed /BuOH (11.1 mL). The suspension was stirred at 45 °C for 15 min, whereupon a freshly prepared /BuOH solution (0.67 mL) containing Pd2dba3 (40.6 mg, 0.044 mmol) and RuPhos (41.5 mg, 0.088 mmol) that had been stirred at 60 °C for 30 min was added. The tube was sealed, and the reaction was stirred at 100 °C for 3 h. After cooling to room temperature, the mixture was filtered through Celite, the filter cake was washed with CH2Q2 (200 mL), and the filtrate was concentrated. The residue was dissolved in CH2C12 (50 mL), washed with saturated aq. NaHC03 (2 x 50 mL), and extracted with 1 N HC1 (4 x 30 mL). The combined acidic aqueous extracts were made basic with 6 N NaOH and extracted with CH2CI2 (4 x 50 mL), after which the combined organic extracts were dried (Na2S04) and concentrated under reduced pressure. The crude material was purified via flash chromatography (S1O2) eluting with CEbCh/MeOH/EtsN (97:2: 1) affording 0.418 g (82%) of 2 as a red oil. NMR (400 MHz, CDC13) δ 7.46 (d, J = 2.8 Hz, 1 H), 7.08 (d, J = 8.4 Hz, 1 H), 7.02 (dd, J = 8.4, 2.8 Hz, 1 H), 3.14 - 3.06 (comp, 4 H), 3.00 - 2.93 (comp, 4 H), 2.79 (t, J = 6.1 Hz, 2 H), 2.70 (br s, 1 H), 2.54 (m, 2 H), 2.01 (m, 2 H); 13C NMR (101 MHz, CDCI3) δ 198.5, 150.3, 135.8, 132.8, 129.4, 122.0, 112.8, 50.0, 45.8, 39.1, 28.7, 23.4; HRMS (ESI) m/z calcd for Ci4Hi8N20 (M+H)+, 231.1492; found 231.1497

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM - WO2017/190107, 2017, A1 Location in patent: Page/Page column 87
[2]Current Patent Assignee: HARVARD UNIVERSITY - WO2018/156883, 2018, A1 Location in patent: Page/Page column 32; 33

84
[ 32281-97-3 ]
[ 2039-88-5 ]
C₁₈H₁₇BrO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran at -78℃;	1 Example 1 Compound A1 prepared by the above reaction for preparing Compound A. Among them, Compound C used was 1-bromo-2-vinylbenzene (11 mmol), and Compound D was 7-bromo-3,4-dihydronaphthalene-1(2H)-one (10 mmol).Tetrahydrofuran (THF) solution was added and n-butyllithium (n-BuLi) was added. The molar ratio of n-butyllithium to compound C was 1.1:1.The reaction was stirred at -78° C. for 1 h to 2 h to give the target compound A1. The specific reaction formula is as follows:
	With n-butyllithium In tetrahydrofuran; ethyl acetate at -78℃;	1 Compound C used in the preparation of compound A1 is 1-bromo-2-vinylbenzene, and compound D is 7-bromo-3,4-dihydronaphthalene-1(2H)-one, compound C pre-compound D molar ratio Mixing 1:1, adding ethyl acetate (EtOAc) solution, and adding n-BuLi catalyst, the molar ratio of n-butyllithium to compound C is 1.1:1. The reaction was stirred at -78°C for 1 h to 2 h to give the target product (A1). The reaction formula is as follows:

Reference： [1]Current Patent Assignee: SOUTHERN UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA - CN107759488, 2018, A Location in patent: Paragraph 0098; 0099; 0101; 0103; 0104; 0107
[2]Current Patent Assignee: SOUTHERN UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA - CN107759598, 2018, A Location in patent: Paragraph 0107-0112

85
[ 32281-97-3 ]
[ 134-81-6 ]
C₂₄H₁₉BrO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With n-butyllithium; diisopropylamine In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: benzil In tetrahydrofuran at -78℃; for 12.5h; Inert atmosphere;	3. Synthesis of 2-(1-hydroxy-2-oxo-1, 2-diphenylethyl) cyclohexan-1-ones General procedure: The reactions were carried out according to a literature method.2 A solution of i-Pr2NH (1.3 mL, 9.1 mmol) and n-BuLi (4.9 mL, 1.6 M in hexane) in THF (15 mL) was stirred at 0° C for 1.5 h. To this solution was added ketone (5 mmol) in THF (3 mL) at 0° C. After stirring for 1 h, Benzil (6.5 mmol) in THF (5 mL) was added at -78° C dropwise via syringe over 0.5 h. After 12 h, the reaction was quenched with saturated NH4Cl. Products were extracted with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a crude mixture, which was purified by silica gel column chromatography (eluent: EtOAc / hexane = 1/20) to afford 1, 3 as white solid.

Reference： [1]Ao, Jun; Liu, Yidong; Jia, Shiqi; Xue, Lu; Li, Dongmei; Tan, Yu; Qin, Wenling; Yan, Hailong [Tetrahedron, 2018, vol. 74, # 4, p. 433 - 440]

86
[ 579-39-5 ]
[ 32281-97-3 ]
C₂₄H₁₇BrF₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With n-butyllithium; diisopropylamine In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: 1,2-bis(4-fluorophenyl)ethane-1,2-dione In tetrahydrofuran at -78℃; for 12.5h; Inert atmosphere;	3. Synthesis of 2-(1-hydroxy-2-oxo-1, 2-diphenylethyl) cyclohexan-1-ones General procedure: The reactions were carried out according to a literature method.2 A solution of i-Pr2NH (1.3 mL, 9.1 mmol) and n-BuLi (4.9 mL, 1.6 M in hexane) in THF (15 mL) was stirred at 0° C for 1.5 h. To this solution was added ketone (5 mmol) in THF (3 mL) at 0° C. After stirring for 1 h, Benzil (6.5 mmol) in THF (5 mL) was added at -78° C dropwise via syringe over 0.5 h. After 12 h, the reaction was quenched with saturated NH4Cl. Products were extracted with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a crude mixture, which was purified by silica gel column chromatography (eluent: EtOAc / hexane = 1/20) to afford 1, 3 as white solid.

Reference： [1]Ao, Jun; Liu, Yidong; Jia, Shiqi; Xue, Lu; Li, Dongmei; Tan, Yu; Qin, Wenling; Yan, Hailong [Tetrahedron, 2018, vol. 74, # 4, p. 433 - 440]

87
[ 32281-97-3 ]
[ 74-89-5 ]
7-bromo-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one; methylamine In methanol for 0.0833333h; Stage #2: With sodium cyanoborohydride; acetic acid In methanol at 20℃;	4 Scheme 3 A solution of 7-bromo-l-tetralone (1.5 g, 6.66 mmol) in 30 mL of MeOH was treated with methyl amine (6.8 mL, 66.6 mmol). After 5 minutes, acetic acid (0.15 mL) was added followed by sodium cyanoborohydride (0.5 g, 8.0 mmol). The reaction mixture was stirred overnight at ambient temperature. MeOH and excess methyl amine in the reaction mixture were removed by vacuo. After that, water and saturated aqueous sodium carbonate solution were added to the reaction mixture followed by extraction with dichloromethane (x2). The organic layers were combined and dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to obtain oil. The oil was purified via flash column chromatography over silica gel using 50% ethyl acetate in hexane as the eluent to afford Compound 35, 7-bromo-N-methyl- l,2,3,4-tetrahydronaphthalen-l-amine (1.0 g, 62%, 4.17 mmol).

Reference： [1]Current Patent Assignee: TAIWANJ PHARMACEUTICALS CO LTD - WO2019/108943, 2019, A1 Location in patent: Paragraph 0129-0131

88
[ 120-72-9 ]
[ 941-69-5 ]
[ 32281-97-3 ]
rac-(6aR,6bR,9aR,14cR)-5,6,6a,6b,8,9a,10,14c-octahydro-2-bromo-8-phenylnaphtho[2,1-c]pyrrolo[3,4-a]carbazole-7,9-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With toluene-4-sulfonic acid In isopropyl alcohol for 72h; Inert atmosphere; Reflux; Darkness;	General procedure for Diels-Alder adduct synthesis General procedure: Compounds 8a-g and 10a-e were prepared as follows: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 1-tetralone (5) (1.33 mL, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-toluenesulfonic acid (0.380 g, 2 mmol, 0.2 eq). 9a-g were prepared similarly: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 4-chromanone (6) (1.482 g, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-TsOH (0.380 g, 2 mmol, 0.2 eq). The reaction mixture was heated at reflux for three days under a nitrogen atmosphere, and in the absence of light. Upon completion, a solid reaction mixture was cooled down and filtered with IPA (15 mL) and water (5 mL). The crude material was triturated with IPA (20 mL) three times in the absence of light to give a solid. If further purification was necessary, recrystallization with a mixture of dichloromethane and pentane was performed. In the case of 6 derivatives (9a-g) solubility was found to be very poor, and thus recrystallization was performed with a mixture of tetrahydrofuran and pentane. Using this procedure 8a-g, 9a-g, and 10a-e were synthesized.

Reference： [1]Noland, Wayland E.; Abzhabarov, Firdavs Z. [Synthetic Communications, 2020, vol. 50, # 2, p. 168 - 176]

89
[ 68843-67-4 ]
[ 32281-97-3 ]
(S)-7-((3-phenyl-4,5-dihydroisoxazol-5-yl)methyl)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; (R)-N-((S)-(2-(di((3R,5R,7R)-adamantan-1-yl)phosphaneyl)-4,5-dimethoxyphenyl)(phenyl)methyl)-N,2-dimethylpropane-2-sulfinamide; sodium t-butanolate In toluene at 65℃; for 12h; Inert atmosphere; Schlenk technique; enantioselective reaction;

Reference： [1]Chen, Mingjie; Li, Wenbo; Wang, Lei; Wang, Yuzhuo; Zhang, Junliang; Zhang, Kenan [Angewandte Chemie - International Edition, 2020, vol. 59, # 11, p. 4421 - 4427][Angew. Chem., 2020, vol. 132, # 11, p. 4451 - 4457,7]

90
[ 32281-97-3 ]
[ 82386-89-8 ]
[ 105-56-6 ]
9-bromo-4-(2-chloro-5-(trifluoromethyl)phenyl)-2-oxo-1,2,5,6-tetrahydrobenzo[h]Quinoline-3-carbonitrile [ No CAS ]

Reference： [1]Drug Design, Development and Therapy,2019,vol. 13,p. 4247 - 4263

91
[ 32281-97-3 ]
[ 67-68-5 ]
2-(7-bromo-1,4-naphthoquinone)methyl sulfide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With iodine at 80℃; for 12h; Inert atmosphere;	5 Example 5Synthesis of 2- (7-bromo-1,4-naphthoquinone) methyl sulfide from 7-bromonone and dimethyl sulfoxide In a tubular reactor, sequentially add 7-bromonone (67.2 mg, 0.3 mmol, 1.0 equiv.) And dimethyl sulfoxide (117.0 mg, 1.5 mmol, 5.0 equiv.)And iodine (114.3 mg, 0.45 mmol, 1.5 equiv.),After being vacuumed and protected by nitrogen, it was placed at 80 ° C and stirred for 12 hours. After the reaction was completed,After cooling to room temperature, 5 mL of saturated aqueous sodium thiosulfate solution was added to the reaction mixture, and extracted 3 times with ethyl acetate (5 * 3 mL). Combine the organic phase,Dry with anhydrous sodium sulfate and spin-dry to obtain the pure product. The product isolation yield was 95%.

Reference： [1]Current Patent Assignee: XINYANG NORMAL UNIVERSITY - CN111116436, 2020, A Location in patent: Paragraph 0017

92
[ 557-21-1 ]
[ 32281-97-3 ]
[ 776328-39-3 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 150℃; for 1h; Inert atmosphere; Sealed tube; Microwave irradiation;	59-1.1 Ethyl 7-(hydroxymethyl)-1,2,3,4-tetrahydronaphthalene-2-carboxylate In a microwave reaction container, tetrakis(triphenylphosphine)palladium(0) (920 mg) and zinc cyanide (2.4 g) were added to a suspension of 7-bromo-3,4-dihydro-2H-naphthalen-1-one (1.8 g) in N,N-dimethylformamide (16 mL), the air in the test tube was purged with nitrogen and the test tube was then sealed, and the mixture was stirred at 150°C for 30 minutes under microwave irradiation. Tetrakis(triphenylphosphine)palladium(0) (460 mg) was further added thereto, the air in the test tube was purged with nitrogen and the test tube was then sealed, and the mixture was stirred at 150°C for 30 minutes under microwave irradiation. The same operations were performed in another container, the obtained reaction solutions from them were combined. Ethyl acetate and water were added to the combined reaction solution, and the resultant mixture was filtered through Celite (registered trademark), and the filtrate was extracted with ethyl acetate. The organic layer was sequentially washed with water and brine, passed through a phase separator, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 3:1 to 2:3) to give a crude product (2.2 g) containing 8-oxo-6,7-dihydro5H-naphthalene-2-carbonitrile as a pale yellow solid.

Reference： [1]Current Patent Assignee: TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - EP3666766, 2020, A1 Location in patent: Paragraph 1002

93
[ 37595-74-7 ]
[ 32281-97-3 ]
7-bromo-3,4-dihydronaphthalen-1-yl trifluoromethanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium hexamethylsilazane In tetrahydrofuran; toluene at -78 - 20℃; Inert atmosphere;	Synthesis of 7-bromo-3,4-dihydronaphthalen-1-yl trifluoromethanesulfonate 7-Bromo-3,4-dihydronaphthalen-1(2H)-one (45.0 g, 200 mmol) and 1,1,1-trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (79.0 g, 220 mmol) were dissolved in dry THF (1000 ml). This was cooled to -78° C. and potassium bis(trimethylsilyl)amide 15% solution in toluene (314 ml, 220 mmol) was added. The reaction mixture was stirred at -78° C. for 3 hours. The reaction mixture was left overnight to warm to room temperature under nitrogen. After all the 7-bromo-3,4-dihydronaphthalen-1(2H)-one was consumed, the reaction was quenched by adding water (50 ml). The crude was then purified by flash chromatography using mixtures of heptane and dichloromethane in a standard silica solid phase to afford 7-bromo-3,4-dihydronaphthalen-1-yl trifluoromethanesulfonate (68.9 g, 193 mmol, 96% yield) as a pale yellow oil.

Reference： [1]Current Patent Assignee: UNIVERSAL DISPLAY CORP - US2020/369699, 2020, A1 Location in patent: Paragraph 0128

94
[ 32281-97-3 ]
[ 635757-93-6 ]
C₁₉H₂₅NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With bis(3,5,3′,5′-dimethoxydibenzylideneacetone)palladium(0); C₄₂H₆₈NO₃PS; caesium carbonate In tert-butyl methyl ether at 30℃; for 48h; Inert atmosphere; enantioselective reaction;

Reference： [1]Chen, Mingjie; Liu, Yu; Tu, Youshao; Wang, Lei; Wang, Yuzhuo; Zhang, Junliang [Chemical Science, 2021, vol. 12, # 23, p. 8241 - 8245]

95
[ 32281-97-3 ]
6-bromo-4-chloro-1,2-dihydronaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetrachloromethane; triphenylphosphine at 20℃; for 5.5h; Inert atmosphere; Reflux;	1-3; 1-3 Chlorination In a nitrogen atmosphere, 10mmol 7-bromo-3,4-dihydronaphthalene-1(2H)-one (2.25g) and 20mmol triphenylphosphine PPh3 (5.24g) were added to 200mmol CCl4 (19.3mL), Stir at room temperature for 30 minutes, and then heat to reflux to continue the reaction for 5 hours. After the reaction, the temperature was lowered to room temperature, and the same amount of n-hexane was added to dilute with CCl4. The precipitated crystals were collected by filtration and washed with n-hexane to obtain 6-bromo-4-chloro-1,2-dihydronaphthalene (yield 75%, 1.83g, 95% purity).

Reference： [1]Current Patent Assignee: JIANGSU LIYUAN MEDICINE - CN112979412, 2021, A Location in patent: Paragraph 0031-0034; 0037-0039; 0042; 0044-0045; 0046-0054

96
[ 32281-97-3 ]
1,7-dibromo-1,2,3,4-tetrahydronaphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With sodium tetrahydridoborate; ethanol at 20℃; Stage #2: With phosphorus tribromide In dichloromethane at 0 - 20℃;	Intermediate 23 l,7~l>ibromo-l,2,3,4~tefrahydronaphtIialene To a solution of 7-bromo-3,4-dihydronaphthalen-l(2/T)-one (200 mg, 0.90 mmol, 1 equiv) in EtOH (4 mL) ws added sodium borohydride (50.4 mg, 1.33 mmol, 1.5 equiv) was added in one portion and stirred at room temperature. Progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was concentrated, dissolved in EtOAc, and washed with water. The organic layer was dried over MgSCE and concentrated. The residue ws dissolved in CH2CI2 (4 ml.) and cooled to 0 °C. PBn (481 mg, 1.78 mmol, 2 equiv) was added dropwise to the reaction mixture. The reaction was warmed to room temperature and followed by TLC. NaHCG (sat.) was added and the mixture was extracted with EtOAc. The combined organic layers were dried over MgSOr and concentrated to give the title compound (263 mg, 0.90 mmol, quant.), which was used in the next step without further purification. lH NMR (400 MHz, Chloroform-**) d 7.49 (d, J= 2. 1 Hz, 1H), 7.28 (dd, J = 8.2, 2.1 Hz, 1H), 6.94 (d, J= 8.2 Hz, 1H), 5.48 (t, J --- 3.8 Hz, i l l). 3.06 -2.70 (m, 4H), 2 38 id. ,/ 14.4 Hz, 111). 2.29 - 2.03 (m. M l). 1.97 (0338) - 1.81 (m, 2H).
	Multi-step reaction with 2 steps 1: sodium tetrahydridoborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 2: phosphorus tribromide / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: VANDERBILT UNIVERSITY - WO2021/92525, 2021, A1 Location in patent: Paragraph 00185-00186
[2]Guo, Rui; Sang, Jiale; Xiao, Haijing; Li, Junxia; Zhang, Guozhu [Chinese Journal of Chemistry, 2022, vol. 40, # 11, p. 1337 - 1345]

97
[ 32281-97-3 ]
[ 126-81-8 ]
[ 4637-24-5 ]
2-bromo-10,10-dimethyl-6,9,10,11-tetrahydrobenzo[c]acridin-8(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With indium(III) triflate; ammonium acetate at 100℃; for 4h;

Reference： [1]Jamshaid, Sana; Lee, Yong Rok; Mohandoss, Sonaimuthu [Green Chemistry, 2021, vol. 23, # 14, p. 5113 - 5119]

98
[ 32281-97-3 ]
[ 4637-24-5 ]
2,12-dibromo-5,6,8,9-tetrahydrodibenzo[c,h]acridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With indium(III) triflate; ammonium acetate at 100℃; for 4h;

Reference： [1]Jamshaid, Sana; Lee, Yong Rok; Mohandoss, Sonaimuthu [Green Chemistry, 2021, vol. 23, # 14, p. 5113 - 5119]

99
[ 32281-97-3 ]
[ 17336-59-3 ]
3,4,6',7'-tetrahydro-[1,2'-binaphthalen]-8'(5'H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 1-tetralone tosylhydrazone With 2,5-Dimethyl-1,4-benzoquinone; palladium diacetate; sodium hydride; triphenylphosphine; bis(pinacol)diborane In toluene at 100℃; for 10h; Inert atmosphere; Schlenk technique; Stage #2: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With sodium hydroxide In toluene at 90℃; for 24h; Inert atmosphere; Schlenk technique;

Reference： [1]Chang, Taiwei; Huo, Jingfeng; Lei, Ming; Ping, Yifan; Wang, Jianbo; Wang, Qianyue; Wang, Rui [Journal of the American Chemical Society, 2021, vol. 143, # 26, p. 9769 - 9780]

100
[ 32281-97-3 ]
[ 107-06-2 ]
8-bromo-4,5-dihydro-1H-benzo[g]indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	Stage #1: 7-bromo-3,4-dihydro-2H-naphthalen-1-one With ammonium hydroxide hydrochloride; potassium hydroxide In dimethyl sulfoxide at 20 - 140℃; for 1h; Stage #2: 1,2-dichloro-ethane In dimethyl sulfoxide at 140℃; for 1h;	2.3 Compound 3.1 (8-bromo-4,5-dihydro-lH-benzo[g]indole): A 250 mL 2 neck round bottom flask was fitted with a finned condenser, stir bar, and gas adapter. The flask was flushed with argon and KOH (85% purity, 60.0 mmol, 4.106 g) and NH2OH.HCI (60.0 mmol, 4.169 g) were added to the flask, immediately followed by anhydrous DMSO (5 mL). This mixture was stirred at room temperature under argon for 5 minutes, then 7-bromo-3,4-dihydronaphthalen-l(2H)-one (50.0 mmol, 11.255 g) was added. The flask was stoppered and stirred at room temperature for 1 minute, then heated to 110 °C in a heat block for 1 hour. More KOH (85% purity, 300 mmol, 16.833 g) was added to the flask and the temperature of the heat block was raised to 140 °C. Anhydrous dichloroethane (200 mmol, 15.8 mL) was diluted to a total volume of 40 mL with anhydrous DMSO. This solution was transferred to a 50 mL syringe and added to the reaction mixture over a period of 30 minutes with very vigorous stirring at 140 °C. More of the dichloroethane/DMSO solution was made and an additional 10 mL of this mixture was added via syringe pump over an additional 30 minutes. The reaction mixture was cooled to 0 °C in an ice- water bath and was quenched with saturated aqueous ammonium chloride (100 mL). This mixture was diluted with water (400 mL) and extracted with ether (250 mL) and ethyl acetate (100 mL). The 2-phase mixture was stirred vigorously at room temperature, then filtered through a pad of celite to remove solids. The aqueous layer was extracted with ether (2 X 200 mL). The combined organic layers were washed with water (5 X 50 mL), brine (50 mL), dried over MgSCU, filtered, and evaporated to dryness. The crude mixture was purified by flash chromatography on silica gel (100% hexanes (1 CV) · 10% DCM/hexanes (1 CV) · 30% DCM/hexanes (9 CV)). Repurified product fractions on silica gel (100% hexanes (1 CV) 1% EtOAc/hexanes 0 CV) 10% EtOAc/hexanes (9 CV)). Product fractions were collected and rotovaped to give 4.507 g, 36% yield. Major impurities include the N-vinyl product and two O-linked, ethylene-bridged oximes. MS (APCI): calculated for Ci2Hi0BrN (M + H) = 248; found: 248.

Reference： [1]Current Patent Assignee: NITTO DENKO CORPORATION - WO2021/146380, 2021, A1 Location in patent: Page/Page column 43; 44

101
[ 32281-97-3 ]
3-oxo-9-hydrazone clarithromycin [ No CAS ]
3-oxo-9-(7-bromo-1-tetralone)hydrazone clarithromycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid In methanol at 20℃; for 2h;	16 Example 16 3-oxo-9-(7-bromo-1-tetralone) hydrazone clarithromycin (SIPI-8681) Add 3-oxo-9-hydrazone clarithromycin (1g, 1.66mmol), 7-bromo-1-tetralone (0.56g, 2.5mmol), glacial acetic acid (0.16g, 2.5mmol) to 10ml methanol middle,The reaction was carried out at room temperature for 2 hours. After the completion of the reaction as monitored by TLC, the reaction mixture was spin-dried.Use 200-300 mesh silica gel for column chromatography to obtain 0.96 g of light yellow solid.The yield was 73.09%, and the HPLC purity was 94.6%.

Reference： [1]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN113121626, 2021, A Location in patent: Paragraph 0225-0227

102
[ 32281-97-3 ]
3-hydroxy-9-hydrazone clarithromycin [ No CAS ]
3-hydroxy-9-(7-bromo-1-tetralone)hydrazone clarithromycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.41%	With acetic acid In methanol at 20℃; for 2h;	29 Example 29 3-hydroxy-9-(7-bromo-1-tetralone) hydrazone clarithromycin (SIPI-8781) Add 3-hydroxy-9-hydrazone clarithromycin (1g, 1.66mmol), 7-bromo-1-tetralone (0.56g, 2.5mmol), and glacial acetic acid (0.16g, 2.5mmol) to 10ml of methanol ,The reaction was carried out at room temperature for 2 hours. After the completion of the reaction as monitored by TLC, the reaction mixture was spin-dried.Use 200-300 mesh silica gel for column chromatography to obtain 1.15 g of light yellow solid.The yield was 87.41%, and the HPLC purity was 96.1%.

Reference： [1]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN113121626, 2021, A Location in patent: Paragraph 0265-0267

103
[ 32281-97-3 ]
B-methoxy-9-BBN [ No CAS ]
[ 6836-19-7 ]

Yield	Reaction Conditions	Operation in experiment
42%	With N<SUP>1</SUP>-(4-hydroxy-2,6-dimethylphenyl)-N<SUP>2</SUP>-(4-hydroxy-3,5-dimethylphenyl)oxalamide; caesium carbonate In 1-methyl-pyrrolidin-2-one at 80℃; for 12h; Inert atmosphere;	13 The method for methoxylation reaction of aryl or heteroaryl of the present invention specifically includes: Mix 0.2mmol substrate, 0.3mmol coupling agent, 0.01mmol ligand, 1mL solvent, 0.01mmol catalyst and 0.4mmol base in an argon atmosphere and react at 80 for 12h to obtain 15mg 7-methoxy-1 -Tetralone is a white solid; the yield of 7-methoxy-1-tetralone is 42%; The structural formula of the substrate is that the coupling agent is MeO-9-BBN; the solvent is N-methylpyrrolidone; the catalyst is cuprous halide; the base is cesium carbonate; the ligand is L3

Reference： [1]Current Patent Assignee: WUYI UNIVERSITY - CN113666826, 2021, A Location in patent: Paragraph 0141-0147

104
[ 32281-97-3 ]
[ 113118-83-5 ]
(E)-7-bromo-2-((5-methoxypyridin-3-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium hydroxide In methanol; water monomer at -5 - 25℃; for 3h;	1-15 General procedure: In the Claisen-Schmidt condensation reaction, 7-methoxy-3,4-dihydronaphthalen-1(2H)-one (500 mg, 2.84 mmol)and 5-methoxy-3-pyridinecarboxaldehyde (389 mg, 2.84 mmol)were dissolved in 10 mL of methanol. A 25% sodium hydroxidesolution was added at 5 C and the reaction was stirred for 3 h atroom temperature. Process control was monitored by silica gel thinlayer chromatography. After completion of the reaction, the residuewas filtered out of the reaction mixture and dissolved indichloromethane. The organic phase was washed with deionizedwater and brine respectively, dried over anhydrous sodium sulphateand condensed under vacuum. Crystals were obtained bysolvent evaporation in a mixture of dichloromethane and methanol (1:1, v/v) under ambient conditions and dried under vacuum at60 C for 3 h. 700 mg of compound 1 was obtained as a white solidin 83.4% yield. Following the above synthetic procedure, compounds2e15 were synthesized. some pure products were obtainedin crystalline form.

Reference： [1]Hou, Gui-Ge; Hou, Yun; Luan, Ming-Zhu; Meng, Qing-Guo; Yan, Wei-Bin; Zhang, Xiao-Fan; Zhao, Feng-Lan [European Journal of Medicinal Chemistry, 2022, vol. 235]

105
[ 65873-72-5 ]
[ 32281-97-3 ]
(E)-7-bromo-2-((6-methoxypyridin-3-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide In methanol; water monomer at -5 - 25℃; for 3h;	1-15 General procedure: In the Claisen-Schmidt condensation reaction, 7-methoxy-3,4-dihydronaphthalen-1(2H)-one (500 mg, 2.84 mmol)and 5-methoxy-3-pyridinecarboxaldehyde (389 mg, 2.84 mmol)were dissolved in 10 mL of methanol. A 25% sodium hydroxidesolution was added at 5 C and the reaction was stirred for 3 h atroom temperature. Process control was monitored by silica gel thinlayer chromatography. After completion of the reaction, the residuewas filtered out of the reaction mixture and dissolved indichloromethane. The organic phase was washed with deionizedwater and brine respectively, dried over anhydrous sodium sulphateand condensed under vacuum. Crystals were obtained bysolvent evaporation in a mixture of dichloromethane and methanol (1:1, v/v) under ambient conditions and dried under vacuum at60 C for 3 h. 700 mg of compound 1 was obtained as a white solidin 83.4% yield. Following the above synthetic procedure, compounds2e15 were synthesized. some pure products were obtainedin crystalline form.

Reference： [1]Hou, Gui-Ge; Hou, Yun; Luan, Ming-Zhu; Meng, Qing-Guo; Yan, Wei-Bin; Zhang, Xiao-Fan; Zhao, Feng-Lan [European Journal of Medicinal Chemistry, 2022, vol. 235]

106
[ 54221-96-4 ]
[ 32281-97-3 ]
(E)-7-bromo-2-((6-methoxypyridin-2-yl)methylene)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydroxide In methanol; water monomer at -5 - 25℃; for 3h;	1-15 General procedure: In the Claisen-Schmidt condensation reaction, 7-methoxy-3,4-dihydronaphthalen-1(2H)-one (500 mg, 2.84 mmol)and 5-methoxy-3-pyridinecarboxaldehyde (389 mg, 2.84 mmol)were dissolved in 10 mL of methanol. A 25% sodium hydroxidesolution was added at 5 C and the reaction was stirred for 3 h atroom temperature. Process control was monitored by silica gel thinlayer chromatography. After completion of the reaction, the residuewas filtered out of the reaction mixture and dissolved indichloromethane. The organic phase was washed with deionizedwater and brine respectively, dried over anhydrous sodium sulphateand condensed under vacuum. Crystals were obtained bysolvent evaporation in a mixture of dichloromethane and methanol (1:1, v/v) under ambient conditions and dried under vacuum at60 C for 3 h. 700 mg of compound 1 was obtained as a white solidin 83.4% yield. Following the above synthetic procedure, compounds2e15 were synthesized. some pure products were obtainedin crystalline form.

Reference： [1]Hou, Gui-Ge; Hou, Yun; Luan, Ming-Zhu; Meng, Qing-Guo; Yan, Wei-Bin; Zhang, Xiao-Fan; Zhao, Feng-Lan [European Journal of Medicinal Chemistry, 2022, vol. 235]

107
[ 32281-97-3 ]
[ 86-81-7 ]
(E)-7-bromo-2-(3,4,5-trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium hydroxide In methanol; water monomer at -5 - 25℃; for 3h;	1-15 General procedure: In the Claisen-Schmidt condensation reaction, 7-methoxy-3,4-dihydronaphthalen-1(2H)-one (500 mg, 2.84 mmol)and 5-methoxy-3-pyridinecarboxaldehyde (389 mg, 2.84 mmol)were dissolved in 10 mL of methanol. A 25% sodium hydroxidesolution was added at 5 C and the reaction was stirred for 3 h atroom temperature. Process control was monitored by silica gel thinlayer chromatography. After completion of the reaction, the residuewas filtered out of the reaction mixture and dissolved indichloromethane. The organic phase was washed with deionizedwater and brine respectively, dried over anhydrous sodium sulphateand condensed under vacuum. Crystals were obtained bysolvent evaporation in a mixture of dichloromethane and methanol (1:1, v/v) under ambient conditions and dried under vacuum at60 C for 3 h. 700 mg of compound 1 was obtained as a white solidin 83.4% yield. Following the above synthetic procedure, compounds2e15 were synthesized. some pure products were obtainedin crystalline form.

Reference： [1]Hou, Gui-Ge; Hou, Yun; Luan, Ming-Zhu; Meng, Qing-Guo; Yan, Wei-Bin; Zhang, Xiao-Fan; Zhao, Feng-Lan [European Journal of Medicinal Chemistry, 2022, vol. 235]

108
[ 32281-97-3 ]
[ 59-88-1 ]
C₁₆H₁₄BrN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With hydrogenchloride In ethanol; lithium hydroxide monohydrate at 90℃; for 12h;	11.a a) Synthesis of intermediate 2-1a Put phenylhydrazinehydrochloride (70.0 g, 484.1 mmol) and 7-bromo-3,4-dihydro-2H-naphthalen-1-one (108.9 g, 484.1 mmol) in a round-bottom flask and dissolve in ethanol (1200 ml).After slowly adding 60 mL of hydrochloric acid dropwise at room temperature, the mixture was stirred at 90° C. for 12 hours.When the reaction is complete, the solvent is removed under reduced pressure, followed by extraction with an excess of EA.The organic solvent was removed under reduced pressure, stirred in a small amount of methanol, and filtered to obtain 95.2 g (66%) of Intermediate 2-1a.

Reference： [1]Current Patent Assignee: SAMSUNG SDI CO.,LTD. - WO2022/55169, 2022, A1 Location in patent: Page/Page column 51

109
[ 591-12-8 ]
[ 32281-97-3 ]
(R)-5-methyl-5-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)furan-2(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With (R)-AntPhos; potassium carbonate; Palladium⁽⁰⁾ bis(dibenzylideneacetone) In tert-Amyl alcohol; ethyl acetate at 80℃; for 40h; Sealed tube; Inert atmosphere; enantioselective reaction;

Reference： [1]Chen, Qiaoyu; Li, Sanliang; Yang, Junfeng; Zhang, Junliang [Angewandte Chemie - International Edition, 2022, vol. 61, # 23][Angew. Chem.]

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Technical Information

• 1,4-Addition of an Amine to a Conjugated Enone • 1,4-Additions of Organometallic Reagents • Acetal Formation • Acid-Catalyzed α -Halogenation of Ketones • Add Hydrogen Cyanide to Aldehydes and Ketones to Produce Alcohols • Addition of a Hydrogen Halide to an Internal Alkyne • Alcohol Syntheses from Aldehydes, Ketones and Organometallics • Alcohols from Haloalkanes by Acetate Substitution-Hydrolysis • Alcohols React with PX3 • Aldehydes and Ketones Form Hemiacetals Reversibly • Aldehydes May Made by Terminal Alkynes Though Hydroboration-oxidation • Aldol Addition • Aldol Condensation • Alkenes React with Ozone to Produce Carbonyl Compounds • Alkyl Halide Occurrence • Alkylation of Aldehydes or Ketones • Alkylation of an Alkynyl Anion • Alkylation of Enolate Ions • An Alkane are Prepared from an Haloalkane • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Base-Catalyzed Hydration of α,β -Unsaturated Aldehydes and Ketones • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Birch Reduction of Benzene • Blanc Chloromethylation • Bucherer-Bergs Reaction • Claisen Condensations Produce β-Dicarbonyl Compounds • Claisen Condensations Produce β-Dicarbonyl Compounds • Clemmensen Reduction • Complete Benzylic Oxidations of Alkyl Chains • Complete Benzylic Oxidations of Alkyl Chains • Conjugated Enone Takes Part in 1,4-Additions • Conversion of Amino with Nitro • Convert Haloalkanes into Alcohols by SN2 • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Cyanohydrins can be Convert to Carbonyl Compounds under Basic Conditions • Decarboxylation of 3-Ketoacids Yields Ketones • Decarboxylation of Substituted Propanedioic • Deoxygenation of the Carbonyl Group • Deprotonation of a Carbonyl Compound at the α -Carbon • Deprotonation of Methylbenzene • Diorganocuprates Convert Acyl Chlorides into Ketones • Directing Electron-Donating Effects of Alkyl • Dithioacetal Formation • Electrophilic Chloromethylation of Polystyrene • Enamines Can Be Used to Prepare Alkylated Aldehydes • Enol-Keto Equilibration • Enolate Ions Are Protonated to Form ketones • Exclusive 1,4-Addition of a Lithium Organocuprate • Fischer Indole Synthesis • Friedel-Crafts Alkylation of Benzene with Acyl Chlorides • Friedel-Crafts Alkylation of Benzene with Carboxylic Anhydrides • Friedel-Crafts Alkylation of Benzene with Haloalkanes • Friedel-Crafts Alkylation Using Alkenes • Friedel-Crafts Alkylations of Benzene Using Alkenes • Friedel-Crafts Alkylations Using Alcohols • Friedel-Crafts Reaction • Furan Hydrolyzes to Dicarbonyl Compounds • Geminal Diols and Acetals Can Be Hydrolyzed to Carbonyl Compounds • General Reactivity • Grignard Reaction • Groups that Withdraw Electrons Inductively Are Deactivating and Meta Directing • Halogenation of Alkenes • Halogenation of Benzene • Hantzsch Pyridine Synthesis • Hemiaminal Formation from Amines and Aldehydes or Ketones • Hemiaminal Formation from Amines and Aldehydes or Ketones • Henry Nitroaldol Reaction • HIO4 Oxidatively Degrades Vicinal Diols to Give Carbonyl Derivatives • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydration of the Carbonyl Group • Hydride Reductions • Hydride Reductions of Aldehydes and Ketones to Alcohols • Hydride Reductions of Aldehydes and Ketones to Alcohols • Hydrogenation by Palladium on Carbon Gives the Saturated Carbonyl Compound • Hydrogenation to Cyclohexane • Hydrogenolysis of Benzyl Ether • Hydrolysis of Imines to Aldehydes and Ketones • Imine Formation from Amines and Aldehydes or Ketones • Isomerization of β, γ -Unsaturated Carbonyl Compounds • Ketone Synthesis from Nitriles • Ketones Undergo Mixed Claisen Reactions to Form β-Dicarbonyl Compounds • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • Lithium Organocuprate may Add to the α ,β -Unsaturated Carbonyl Function in 1,4-Fashion • Mannich Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mercury Ions Catalyze Alkynes to Ketones • Methylation of Ammonia • Methylation of Ammonia • Michael Addition • Nitration of Benzene • Nucleophilic Aromatic Substitution • Nucleophilic Aromatic Substitution with Amine • Oxidation of Alcohols to Carbonyl Compounds • Oxidation of Alkyl-substituted Benzenes Gives Aromatic Ketones • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Phenylhydrazone and Phenylosazone Formation • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Pyrroles, Furans, and Thiophenes are Prepared from γ-Dicarbonyl Compounds • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reductive Amination • Reductive Amination • Reductive Removal of a Diazonium Group • Reformatsky Reaction • Reverse Sulfonation——Hydrolysis • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Strecker Synthesis • Substitution and Elimination Reactions of Alkyl Halides • Sulfonation of Benzene • Suzuki Coupling • Tebbe Olefination • The Acylium Ion Attack Benzene to Form Phenyl Ketones • The Claisen Rearrangement • The Nitro Group Conver to the Amino Function • The Reaction of Alkynyl Anions with Carbonyl Derivatives • The Wittig Reaction • Thiazolium Salt Catalysis in Aldehyde Coupling • Thiazolium Salts Catalyze Aldehyde Coupling • Thiazolium Salts Catalyze Aldehyde Coupling • Ugi Reaction • Use 1,3-dithiane to Prepare of α-Hydroxyketones • Vilsmeier-Haack Reaction • Williamson Ether Syntheses • Wittig Reaction • Wolff-Kishner Reduction

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Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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[ CAS No. 32281-97-3 ] {[proInfo.proName]}

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[ 32281-97-3 ] Synthesis Path-Upstream 1~7

[ 32281-97-3 ] Synthesis Path-Downstream 1~109

Technical Information

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[ 32281-97-3 ]

Aryls

Bromides

Ketones

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
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P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
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P263	Avoid contact during pregnancy/while nursing.
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P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
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P305	IF IN EYES:
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P321
P322
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P378
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P391	Collect spillage. Hazardous to the aquatic environment
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P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
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P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
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P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
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P411
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P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 32281-97-3 ] {[proInfo.proName]}

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[ 32281-97-3 ] Synthesis Path-Upstream 1~7

[ 32281-97-3 ] Synthesis Path-Downstream 1~109

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Aryls

Bromides

Ketones

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[ 32281-97-3 ]