[ CAS No. 1007-15-4 ] {[proInfo.proName]}

Name: 1007-15-4|3'-Bromo-4'-fluoroacetophenone|98%
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Quality Control of [ 1007-15-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1007-15-4 ]

Product Details of [ 1007-15-4 ]

CAS No. :	1007-15-4	MDL No. :	MFCD00042466
Formula :	C₈H₆BrFO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SZDWTGAORQQQGY-UHFFFAOYSA-N
M.W :	217.04	Pubchem ID :	70508
Synonyms :

Calculated chemistry of [ 1007-15-4 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	44.29
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) :	-5.92 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.03
Log Po/w (XLOGP3) :	2.4
Log Po/w (WLOGP) :	3.21
Log Po/w (MLOGP) :	2.94
Log Po/w (SILICOS-IT) :	3.25
Consensus Log Po/w :	2.76

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.04
Solubility :	0.2 mg/ml ; 0.000922 mol/l
Class :	Soluble
Log S (Ali) :	-2.4
Solubility :	0.864 mg/ml ; 0.00398 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.87
Solubility :	0.0291 mg/ml ; 0.000134 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.52

Safety of [ 1007-15-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1007-15-4 ]

* 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 [ 1007-15-4 ]
Downstream synthetic route of [ 1007-15-4 ]

[ 1007-15-4 ] Synthesis Path-Upstream 1~10

1
[ 1007-15-4 ]
[ 27407-11-0 ]

Reference： [1] Patent: EP1204659, 2003, B1,

2
[ 1007-15-4 ]
[ 1007-16-5 ]

Yield	Reaction Conditions	Operation in experiment
88%	With Oxone; trifluoroacetic acid In 1,4-dioxane for 10 h; Reflux; Green chemistry	General procedure: To a mixture of acetophenone (100 mg, 1 equiv) or phenylacetylene (1 equiv) in dioxane (5 mL), Oxone (2 equiv) and TFA (2 equiv) were added. The mixture was then heated to reflux for 10 h and then cooled to r.t. H₂O (10 mL) was added and the mixture was extracted with EtOAc (2 × 20 mL). The combined organic layers were treated with sat. NaHCO₃ solution and the aqueous layer was poured onto crushed ice and treated with 2 M HCl; a colorless solid precipitated out. The precipitate was filtered off and dried in vacuo to give benzoic acid (3a) after column chromatography (silica gel; EtOAc–hexane, 1:9) as a white crystalline solid; yield: 0.096 g (95percent) from 1a; mp 122–123 °C.

Reference： [1] Synthesis (Germany), 2015, vol. 47, # 20, p. 3161 - 3168

3
[ 403-42-9 ]
[ 176548-69-9 ]
[ 1007-15-4 ]

Yield	Reaction Conditions	Operation in experiment
28%	Stage #1: at 70 - 90℃; for 5.83333 h; Stage #2: With water In tert-butylmethyl ether	EXAMPLE A5(3,5-dibromo-4-fluorophenyl)-ethanone and (3-bromo-4-fluorophenyl)-ethanone69 g (0.5 mol) of p-fluoroacetophenone were added dropwise to 200.0 g (1.5 mol) of finely powdered aluminium chloride with stirring, during which time the mixture heated up to 70° C. It was kept at 75-80° C. for another 20 minutes and then 184 g (1.15 mol) of bromine were added at this temperature within 2.5 hours. Finally, the resulting mixture was heated to 90° C. for another 3 hours. After being cooled and decolorised the mixture was divided between water and tert.butylmethyl ether. Working up the organic phase yielded 130 g of a brownish-black oil which was separated into 2 fractions on silica gel using toluene as eluant: a) 41.2 g (28percent of theoretical) of colourless crystals, m.p. 59-62° C. and R_f=0.53 (toluene), which were identified as 1-(3,5-dibromo-4-fluorophenyl)-1-ethanone by spectroscopy. IR (KBr):1685 (CO) cm^-1 MS:M⁺ = 294/296/298 (Br₂) b) 46.0 g (42percent of theoretical) of colourless crystals, m.p. 52-55° C. and R_f=0.41 (toluene), which were identified as 1-(3-bromo-4-fluorophenyl)-1-ethanone by spectroscopy. IR (KBr):1682 (CO) cm^-1 MS:M⁺ = 216/218 (Br)

Reference： [1] Patent: US7230001, 2007, B1, . Location in patent: Page/Page column 67-68

4
[ 1220124-55-9 ]
[ 1007-15-4 ]

Reference： [1] Patent: WO2013/28474, 2013, A1, . Location in patent: Page/Page column 53

5
[ 1220124-55-9 ]
[ 676-58-4 ]
[ 1007-15-4 ]

Reference： [1] Patent: WO2013/90271, 2013, A1, . Location in patent: Page/Page column 55

6
[ 1220124-55-9 ]
[ 75-16-1 ]
[ 1007-15-4 ]

Reference： [1] Patent: EP2744499, 2016, B1, . Location in patent: Paragraph 0141

7
[ 1007-16-5 ]
[ 1007-15-4 ]

Reference： [1] Patent: WO2013/90271, 2013, A1,
[2] Patent: WO2013/28474, 2013, A1,
[3] Patent: EP2744499, 2016, B1,

8
[ 1007-15-4 ]
[ 288309-07-9 ]

Reference： [1] Patent: US6399627, 2002, B1,
[2] Patent: WO2013/28474, 2013, A1, . Location in patent: Page/Page column 53

9
[ 1007-15-4 ]
[ 288309-07-9 ]

Reference： [1] Patent: WO2013/90271, 2013, A1, . Location in patent: Page/Page column 55
[2] Patent: EP2744499, 2016, B1, . Location in patent: Paragraph 0141

10
[ 1007-15-4 ]
[ 900175-01-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: With sodium tetrahydroborate In tetrahydrofuran; methanol at 70℃; for 1 h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol at 20℃;	[00318] To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46 mmol) inTHF (100 mL) and methanol (1.0 mL) was added sodium borohydride (2.1 g, 55.5 mmol). The mixture was heated up to 70° C for 1 h, then cooled down to rt. The reaction was quenched by 100 ml of IN HCl solution and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine, dried over MgSC^, and concentrated. The crude product was purified by column chromatography to give 9.8 g of 84A (97percent yield). ¹H NMR (400 MHz, CDCl₃) δ ppm 1.48 (d, J=6.15 Hz, 3 H) 7.24 - 7.33 (m, 1 H) 7.59 (dd, J=6.59, 2.20 Hz, 1 H).
97%	With sodium tetrahydroborate In tetrahydrofuran; methanol at 70℃; for 1 h;	To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46 mmol) in THF (100 mL) and methanol (1.0 mL) was added sodium borohydride (2.1 g, 55.5 mmol). The mixture was heated up to 70° C. for 1 h, then cooled down to rt. The reaction was quenched by 100 ml of 1 N HCl solution and extracted by EtOAc (3.x.100 mL). The combined organic layer was washed by brine, dried over MgSO₄, and concentrated. The crude product was purified by column chromatography to give 9.8 g of 89A (97percent yield). ¹H NMR (400 MHz, CDCl₃) δ ppm 1.48 (d, J=6.15 Hz, 3 H) 7.24-7.33 (m, 1 H) 7.59 (dd, J=6.59, 2.20 Hz, 1 H).

Reference： [1] Patent: WO2006/76246, 2006, A2, . Location in patent: Page/Page column 155
[2] Patent: US2007/3539, 2007, A1, . Location in patent: Page/Page column 80
[3] Tetrahedron Letters, 2007, vol. 48, # 31, p. 5471 - 5474
[4] European Journal of Organic Chemistry, 2011, # 23, p. 4409 - 4414
[5] Patent: WO2018/81047, 2018, A1, . Location in patent: Page/Page column 185

[ 1007-15-4 ] Synthesis Path-Downstream 1~88

1
[ 1007-15-4 ]
[ 900175-01-1 ]

Yield	Reaction Conditions	Operation in experiment
97%		[00318] To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46 mmol) inTHF (100 mL) and methanol (1.0 mL) was added sodium borohydride (2.1 g, 55.5 mmol). The mixture was heated up to 70 C for 1 h, then cooled down to rt. The reaction was quenched by 100 ml of IN HCl solution and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine, dried over MgSC^, and concentrated. The crude product was purified by column chromatography to give 9.8 g of 84A (97% yield). 1H NMR (400 MHz, CDCl3) delta ppm 1.48 (d, J=6.15 Hz, 3 H) 7.24 - 7.33 (m, 1 H) 7.59 (dd, J=6.59, 2.20 Hz, 1 H).
97%	With sodium tetrahydroborate; In tetrahydrofuran; methanol; at 70℃; for 1h;	To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46 mmol) in THF (100 mL) and methanol (1.0 mL) was added sodium borohydride (2.1 g, 55.5 mmol). The mixture was heated up to 70 C. for 1 h, then cooled down to rt. The reaction was quenched by 100 ml of 1 N HCl solution and extracted by EtOAc (3×100 mL). The combined organic layer was washed by brine, dried over MgSO4, and concentrated. The crude product was purified by column chromatography to give 9.8 g of 89A (97% yield). 1H NMR (400 MHz, CDCl3) delta ppm 1.48 (d, J=6.15 Hz, 3 H) 7.24-7.33 (m, 1 H) 7.59 (dd, J=6.59, 2.20 Hz, 1 H).
	With methanol; sodium tetrahydroborate; at 20℃; for 2h;	To a solution of l-(3-bromo-4-fluorophenyl)ethanone (400 mg, 1.84 mmol) in methanol (20 mL) was added sodium borohydride (141 mg, 3.73 mmol). The resulting mixture was stirred at rt for 2 h. The reaction was quenched with water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over Na2S04, filtered and concentrated. The residue obtained was purified by flash column chromatography on silica gel (0-20% EtO Ac/petroleum ether) to afford compound 52a as a yellow oil. Mass Spectrum (LCMS, ESI pos.): Calcd. for CsHsBrFO: 202.8 (M-OH)+; found: 202.8.

Reference： [1]Patent: WO2006/76246,2006,A2 .Location in patent: Page/Page column 155
[2]Patent: US2007/3539,2007,A1 .Location in patent: Page/Page column 80
[3]Tetrahedron Letters,2007,vol. 48,p. 5471 - 5474
[4]European Journal of Organic Chemistry,2011,p. 4409 - 4414
[5]Patent: WO2018/81047,2018,A1 .Location in patent: Page/Page column 185

2
[ 1007-15-4 ]
[ 796061-07-9 ]
1-(9-tosyl-9H-carbazol-3-yl)ethanone [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896

3
[ 1007-15-4 ]
[ 191171-55-8 ]
C₁₄H₁₂NOF [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896

4
[ 1007-15-4 ]
[ 159624-15-4 ]
C₁₉H₂₀NO₃F [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896

5
N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]
[ 1007-15-4 ]
C₁₆H₁₄NO₂F [ No CAS ]
C₁₄H₁₂NOF [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896

6
[ 1007-15-4 ]
[ 73183-34-3 ]
[ 765916-70-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; In 1,4-dioxane; dimethyl sulfoxide;	1-[4-Fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]ethanone To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46.07 mmol) and bis(pinacolato)diboron (12.87 g, 50.68 mmol) in 1,4-dioxane (90 ml) and DMSO (10 ml) was added potassium acetate (9.04 g, 92.14 mmol) and the mixture degassed for 1 h. Dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane (DCM) adduct (1.13 g, 1.38 mmol) was added and the mixture degassed for a further 15 min and then heated at 90 C. for 18 h. After cooling to ambient temperature the mixture was filtered and the filter cake washed with ethyl acetate (2*50 ml). The filtrate was then washed with water (100 ml), brine (100 ml), dried (MgSO4), filtered and evaporated to give the title product as a brown oil which was used without further purification (12.0 g): deltaH (400 MHz, CDCl3) 1.38 (12H, s), 2.61 (2H, s), 2.61 (3H, s), 7.10 (1H, t, J 8.6 Hz), 8.05-8.09 (1H, m), 8.35 (1H, dd, J 2.3, 5.5 Hz).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 110℃; for 0.166667h;Microwave irradiation;	General procedure: To 2 mL of 1,4-dioxane in microwave reaction vessel were added bromobenzene (0.20 g, 1.27 mmol), bis(pinacolato)diboron (0.36 g, 1.40 mmol), potassium acetate (0.38 g, 3.8 mmol), and PdCl2(dppf) (0.028 g, 0.038 mmol). The reaction mixture was heated to 110 C by microwave irradiation at power 100 W for 10 min. After solvent was removed under reduced pressure, the residue was purified by dry column vacuum chromatography (DCVC) using dichloromethane (DCM) as eluent provided the 0.16 g in 62 % yield;

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896
[2]Patent: US2004/192692,2004,A1
[3]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2513 - 2517

7
C₁₄H₁₇NBO₃F₃ [ No CAS ]
[ 1007-15-4 ]
C₁₆H₁₁NO₂F₄ [ No CAS ]
C₁₄H₁₂NOF [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896

8
N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-methane-sulfonamide [ No CAS ]
[ 1007-15-4 ]
[ 959961-62-7 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4893 - 4896

9
[ 37746-78-4 ]
[ 1007-15-4 ]
ethyl (2RS,3SR)-3-(3-bromo-4-fluorophenyl)-3-hydroxy-2-vinylbutyrate [ No CAS ]
ethyl (2SR,3SR)-3-(3-bromo-4-fluorophenyl)-3-hydroxy-2-vinylbutyrate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 10264 - 10267

10
[ 1007-15-4 ]
(R)-1-acetoxy-1-(3-bromo-4-fluorophenyl)ethane [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 5471 - 5474

11
[ 1007-15-4 ]
1-(4-fluoro-3-morpholin-4-yl-phenyl)-ethylamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728

12
[ 1007-15-4 ]
[ 591742-65-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728

13
[ 1007-15-4 ]
1-(4-fluoro-3-morpholin-4-yl-phenyl)-ethanone oxime [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728

14
[ 1007-15-4 ]
[ 591742-64-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728

15
[ 1007-15-4 ]
[(R)-1-(4-Fluoro-3-morpholin-4-yl-phenyl)-ethyl]-((S)-1-phenyl-ethyl)-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728

16
[ 1007-15-4 ]
[ 591742-63-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1725 - 1728

17
[ 1007-15-4 ]
[ 68504-85-8 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 785 - 794

18
[ 1007-15-4 ]
[ 260975-10-8 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 785 - 794

19
[ 1007-15-4 ]
[ 210826-74-7 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 785 - 794

20
[ 1007-15-4 ]
[ 260975-13-1 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 785 - 794

21
[ 1007-15-4 ]
CP-452759 [ No CAS ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 785 - 794

22
[ 1007-15-4 ]
CP-470947 [ No CAS ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 785 - 794

23
[ 1007-15-4 ]
[ 927-74-2 ]
[ 467420-81-1 ]

Yield	Reaction Conditions	Operation in experiment
85%Chromat.	With bis-triphenylphosphine-palladium(II) chloride; triethylamine; triphenylphosphine;copper(l) iodide; In tetrahydrofuran; at 20℃; for 240h;	10.00 9 (46.1 mmol) of 3-bromo-4-fluoroacetophenone, 4.84 g (69.1 mmol) of 1-butyn-3-ol, 1.62 g (2.3 mmol) of bis(triphenylphosphine)palladium(ll) chloride, 0.30 g (1.2 mmol) of triphenylphosphine and 6.99 g (69.1 mmol) of triethylamine in 200 ml of tetrahydrofuran was stirred for 20 min. 0.11 g (0.6 mmol) of copper(l) iodide was then added. The reaction mixture was stirred at room temperature for 10 days. The solvent was distilled off using a rotary evaporator, the residue was taken up in ethyl acetate and the organic phase was extracted with water. The aqueous phase was then extracted twice with ethyl acetate, and the organic phase was then dried and freed from the solvent using a rotary evaporator. Chromatographic purification gave 8.10 g (85% yield) of the desired product as the brown oil.

Reference： [1]Patent: US2003/224942,2003,A1 .Location in patent: Page 15

24
[ 1007-15-4 ]
[ 435273-49-7 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In dichloromethane; acetic acid; at 10℃; for 0.25h;	Step 1: To 3?-bromo-4?-fluoroacetophenone (3.00 g, 13.8 mmol) in CH2Cl2 (15 ml) and acetic acid (0.5 ml) at 10 C. add dropwise bromine (2.43 g, 15.2 mmol) in CH2Cl2 (20 ml). Stir 15 min and concentrate to obtain the crude bromide as a yellow oil
	With bromine; acetic acid; In dichloromethane; at 10℃; for 0.25h;	To <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (3.00 g, 13.8 mmol) in CH2Cl2 (15 ml) and acetic acid (0.5 ml) at 10 C. add dropwise bromine (2.43 g, 15.2 mmol) in CH2Cl2 (20 ml). Stir 15 min and concentrate to obtain the crude bromide as a yellow oil.
	With bromine; In dichloromethane; acetic acid; at 10℃; for 0.25h;	Step 1: To <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (3.00 g, 13.8 mmol) in CH2Cl2 (15 ml) and acetic acid (0.5 ml) at 10 C. add dropwise bromine (2.43 g, 15.2 mmol) in CH2Cl2 (20 ml). Stir 15 min and concentrate to obtain the crude bromide as a yellow oil.

Reference： [1]Patent: US2004/220194,2004,A1 .Location in patent: Page 46
[2]Patent: US2005/239795,2005,A1 .Location in patent: Page/Page column 38
[3]Patent: US2007/66620,2007,A1 .Location in patent: Page/Page column 13

25
[ 1007-15-4 ]
[ 286836-26-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; for 30h;Heating / reflux;	A solution of 1.09 gm (5 mMol) 3-bromo-4-fluoroacetophenone and 3.45 gm (20 mMol) m-chloroperbenzoic acid (70%) in 15 mL dichloromethane was heated at reflux for 18 hours. An additional 3.45 gm m-chloroperbenzoic acid were added and reflux continued for about 12 hours. At this point an additional 1.4 gm m-chloroperbenzoic acid were added and reflux continued for 18 hours. The reaction mixture was cooled to room temperature and was then diluted with 50 mL diethyl ether. The resulting mixture was cooled to 0 C. and was then treated with 15 mL 20% aqueous sodium thiosulfate. The resulting slurry was stirred for about 1 hour and then the phases separated. The organic phase was washed sequentially with 3×20 mL 20% aqueous sodium thiosulfate followed by 3×20 mL saturated aqueous sodium chloride. The organic phase was then dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 10:1 hexane:diethyl ether. Fractions containing product were combined and concentrated under reduced pressure to provide 68% of the desired compound.
68%	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; water; for 48h;Heating / reflux;	A solution of 1.09 gm (5 mMol) 3-bromo-4-fluoroacetophenone and 3.45 gm (20 mMol) m-chloroperbenzoic acid (70%) in 15 mL dichloromethane was heated at reflux for 18 hours. An additional 3.45 gm m-chloroperbenzoic acid were added and reflux continued for about 12 hours. At this point an additional 1.4 gm m-chloroperbenzoic acid were added and reflux continued for 18 hours. The reaction mixture was cooled to room temperature and was then diluted with 50 mL diethyl ether. The resulting mixture was cooled to 0C and was then treated with 15 mL 20% aqueous sodium thiosulfate. The resulting slurry was stirred for about 1 hour and then the phases separated. The organic phase was washed sequentially with 3 x 20 mL 20% aqueous sodium thiosulfate followed by 3 x 20 mL saturated aqueous sodium chloride. The organic phase was then dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 10:1 hexane:diethyl ether. Fractions containing product were combined and concentrated under reduced pressure to provide 68% of the desired compound
	With 3-chloro-benzenecarboperoxoic acid; In water; 1,2-dichloro-ethane; at 85℃; for 49h;	Step 1: Combine 3?-bromo-4?-fluoroacetophenone (2.17 g, 10.0 mmol) and 3-chloroper-benzoic acid (70%, 2.46 g, 10 mmol) in 1,2-dichloroethane (20 ml). Heat at 75 C. for 5 h and add more peracid (0.82 g). Heat an additional 24 h, allow to cool, and filter. Add more peracid (1.64 g) and heat at 85 C. for 20 h. Allow to cool, filter, and wash the filtrate with 1N NaHCO3. Concentrate and partition with ether and 1N NaOH. Wash with brine, dry (MgSO4) and concentrate to obtain the ester as a light yellow solid, m.p. 48-51.

Reference： [1]Patent: US7045545,2006,B1 .Location in patent: Page/Page column 31
[2]Patent: EP1204659,2003,B1 .Location in patent: Page/Page column 23
[3]Patent: US2004/220194,2004,A1 .Location in patent: Page 19; 20

26
[ 1007-15-4 ]
C₈H₈BrFO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole; In tetrahydrofuran; at -78 - -20℃; for 5.5h;	Step 1: To (R)-2-methyl-CBS-oxazaborolidine (1.0M in toluene, 7.1 ml, 7.1 mmol) add BH3.Me2S (2.0M in THF, 3.0 ml, 6.0 mmol). Stir 0.5 h and cool to ?78 C. Add 3?-bromo-4?-fluoroacetophenone (1.50 g, 6.9 mmol). Allow to warm to ?20 C. and stir 5 h at ?20 C. Add slowly MeOH (20 ml). Concentrate and chromatograph on silica to obtain the alcohol as a colorless oil
		To (R)-2-methyl-CBS-oxazaborolidine (1.0M in toluene, 7.1 ml, 7.1 mmol) add BH3.Me2S (2.0M in THF, 3.0ml, 6.0mmol). Stir 0.5 h and cool to -78 C. Add <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (1.50 g, 6.9 mmol). Allow to warm to -20 C. and stir 5 h at -20 C. Add slowly MeOH (20 ml). Concentrate and chromatograph on silica to obtain the alcohol as a colorless oil.
		Step 1: To (R)-2-methyl-CBS-oxazaborolidine (1.0M in toluene, 7.1 ml, 7.1 mmol) add BH3·Me2S (2.0M in THF, 3.0 ml, 6.0 mmol). Stir 0.5 h and cool to -78 C. Add <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong>(1.50 g, 6.9 mmol). Allow to warm to -20 C. and stir 5 h at -20 C. Add slowly MeOH (20 ml). Concentrate and chromatograph on silica to obtain the alcohol as a colorless oil.

Reference： [1]Patent: US2004/220194,2004,A1 .Location in patent: Page 41
[2]Patent: US2005/239795,2005,A1 .Location in patent: Page/Page column 33
[3]Patent: US2007/66620,2007,A1 .Location in patent: Page/Page column 12

27
[ 1007-15-4 ]
[ 288309-07-9 ]

Yield	Reaction Conditions	Operation in experiment
	In hexane; water; ethyl acetate; N,N-dimethyl-formamide;	A. Preparation of 3-cyano-4-fluoroacetophenone. A solution of 3-bromo-4-fluoroacetophenone (1.09 g, 5.00 mmol) and copper(I) cyanide (0.90 g, 10.0 mmol) in anhydrous DMF (15 mL) was heated at 120 C overnight. Water and EtOAc were added. The solution was filtered. Organic phase was separated, washed with sat. NaCl, dried over Na2SO4, concentrated in vacuo to give an oil, which was purified by a silica gel column using a gradient of 0-20% EtOAc in hexane as solvents, to give the titled compound (0.242 g, yield: 30%). MS 164 (M+H).
	With copper(I) cyanide; In N,N-dimethyl-formamide; for 10h;Inert atmosphere; Reflux;	Step C: 5-acetyl-2-fluorobenzonitrile; A solution of 1-(3-bromo-4-fluorophenyl)ethanone (81.3g, 0.344 mol) in 300 mL ofDMF was added CuCN (67.4 g, 0.749 mol) and the mixture washeated to reflux and stirred under N2 for 10 h. The reaction mixture was quenched with waterand extracted with ether. The organic layer was washed with brine dried over Na2S04 and concentrated in vacuum. The residue was purified with silica gel cloumn chromatography togive the product 5-acetyl-2-fluorobenzonitrile.

Reference： [1]Patent: US6399627,2002,B1
[2]Patent: WO2013/28474,2013,A1 .Location in patent: Page/Page column 53

28
[ 1007-15-4 ]
[ 616-38-6 ]
methyl 3-[3-(bromo)-4-(fluoro)-phenyl]-3-oxopropionate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.0 g (26%)	In tetrahydrofuran; mineral oil;	Methyl 3-[3-(bromo)-4-(fluoro)-phenyl]-3-oxopropionate To a suspension of sodium hydride (1.1 g of 60% suspension in mineral oil, hexane-washed, 27.6 mmol) in 50 mL of tetrahydrofuran was added dimethyl carbonate (2.3 mL, 27.6 inmol) and <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (3.0 g, 13.8 mmol). The resulting suspension was stirred at 65 C. for 1 h and then was cooled to room temperature. The reaction mixture was diluted with ethyl acetate and washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (elution with 3:1 hexane/ethyl acetate) to afford 1.0 g (26%) of the title compound. 1 H NMR (CDCl3) (data for keto tautomer) delta8.15 (dd, 1H), 7.87 (m, 1H), 7.2 (m, 1H), 3.95 (s, 2H), 3.73 (s, 3H).

Reference： [1]Patent: US5998424,1999,A

29
[ 1007-15-4 ]
N-hydroxy-N-(1-(3-bromo-4-fluorophenyl)-ethyl)-urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 122 Preparation of N-Hydroxy-N-(1-(3-bromo-4-fluorophenyl) ethyl) urea The compound was prepared using the method of Example 97 substituting 3-bromo-4-fluoroacetophenone for p-bromoacetophenone. mp 125-7 C.; IR (KBr) 3460, 3300, 1660, 1630, 1495 cm-1; 1 H NMR (d6 Me2 SO) 1.39 (d, 3, J=7 Hz), 5.28 (q, 1, J=7 Hz), 6.39 (bs, 2), 7.30 (t, 1, J=8 Hz), 7.34 (dt, 1, J=2,8 Hz), 7.62 (dd, 1, J=2,7 Hz), 9.18 (s,1) ppm; mass spectrum m/e 294 and 296 (M+ +NH4), 278 and 280 (M+ +H). Analysis calculated for C9 H10 BrFN2 O2: C, 39.01, H 3.64, N, 10.11; found: C, 39.14, H, 3.68, N, 10.15.

Reference： [1]Patent: US5185363,1993,A

30
[ 1007-15-4 ]
[ 624-83-9 ]
N-hydroxy-N-(1-(3-bromo-4-fluorophenyl)ethyl)-N'-methyl urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 114 Preparation of N-Hydroxy-N-(1-(3-bromo-4-fluorophenyl)ethyl)-N'-methyl urea The compound was prepared using the method of Example 97 substituting 3-bromo-4-fluoroacetophenone for p-bromoacetophenone, and substituting methyl isocyanate for trimethylsilyl isocyanate. mp 137-8 C.; IR (KBr) 3370, 3240, 1640, 1530, 1495 cm-1; 1 H NMR (d6 Me2 SO) 1.38 (d, 3, J=7 Hz), 2.57 (d, 3, J=4.5 Hz), 5.26 (q, 1, J=7 Hz), 6.91 (q, 1, J=4.5 Hz), 7.30 (t, 1, J=8 Hz), 7.33 (ddt, 1, J=2, 5, 9 Hz), 7.61 (dd, 1, J=2, 7 Hz), 9.09 (s,1) ppm; mass spectrum m/e (rel intensity) 308 and 310 (43, M+ +NH4), 294 (85), 292 (100), 275 (60). Analysis calculated for C10 H12 BrFN2 O2: C, 41.26, H, 4.15, N, 9.62; found: C, 41.46, H, 4.12, N, 9.68.

Reference： [1]Patent: US5185363,1993,A

31
[ 1007-15-4 ]
[ 99-61-6 ]
[ 218627-10-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In ethanol;	EXAMPLE 84 3-[5-[3-[3-[(aminoiminomethyl)amino]phenyl]-1-oxopropenyl]-2-fluorophenyl]propenoic acid, trifluoroacetate salt STR260 Step A STR261 To a solution of 3-bromo-4-fluoroacetophenone (20.0 g, 92.2 mmoles) and 3-nitrobenzaldehyde (13.9 g, 92.2 mmoles) in absolute ethanol (92 mL) was added slowly a solution of potassium hydroxide (1.18 g, 21.1 mmoles) in absolute ethanol (8 mL), forming a thick paste. The mixture was diluted with ethanol (100 mL), and then stirred overnight in a stoppered flask. The solid was filtered, washed with ethanol, and then air dried to give the above compound (30.3 g), as a pale yellow solid. 1 H NMR was consistent with the proposed structure.
	With potassium hydroxide; In ethanol;	Example 84 3-[5-[3-[3-[(aminoiminomethyl)amino]phenyl]-1-oxopropenyl]-2-fluorophenyl]propenoic acid, trifluoroacetate salt To a solution of 3-bromo-4-fluoroacetophenone (20.0 g, 92.2 mmoles) and 3-nitrobenzaldehyde (13.9 g, 92.2 mmoles) in absolute ethanol (92 mL) was added slowly a solution of potassium hydroxide (1.18 g, 21.1 mmoles) in absolute ethanol (8 mL), forming a thick paste. The mixture was diluted with ethanol (100 mL), and then stirred overnight in a stoppered flask. The solid was filtered, washed with ethanol, and then air dried to give the above compound (30.3 g), as a pale yellow solid. 1H NMR was consistent with the proposed structure. The above compound was prepared as in Example 5, Step A starting with the product of Step A. 1H NMR was consistent with the proposed structure. The above compound was prepared as in Example 5, Steps C-E starting using the product of Step B.

Reference： [1]Patent: US5852210,1998,A
[2]Patent: EP894084,2002,B1

32
aqueous sodium chloride [ No CAS ]
[ 1007-15-4 ]
sodium thiosulfate [ No CAS ]
[ 937-14-4 ]
[ 286836-26-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	In dichloromethane;	O-acetyl 3-bromo-4-fluorophenol A solution of 1.09 gm (5 mMol) 3-bromo-4-fluoroacetophenone and 3.45 gm (20 mMol) m -chloroperbenzoic acid (70%) in 15 mL dichloromethane was heated at reflux for 18 hours. An additional 3.45 gm m -chloroperbenzoic acid were added and reflux continued for about 12 hours. At this point an additional 1.4 gm m -chloroperbenzoic acid were added and reflux continued for 18 hours. The reaction mixture was cooled to room temperature and was then diluted with 50 mL diethyl ether. The resulting mixture was cooled to 0C and was then treated with 15 mL 20% aqueous sodium thiosulfate. The resulting slurry was stirred for about 1 hour and then the phases separated. The organic phase was washed sequentially with 3 x 20 mL 20% aqueous sodium thiosulfate followed by 3 x 20 mL saturated aqueous sodium chloride. The organic phase was then dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluding with 10:1 hexane:diethyl ether. Fractions containing product were combined and concentrated under reduced pressure to provide 68% of the desired compound.

Reference： [1]Patent: EP1204654,A1
Patent: ,2002,

33
[ 1007-15-4 ]
[ 929884-63-9 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: To iodobenzene diacetate (5.34 g, 16.6 mmol) in CH3CN (140 ml) add trifluoromethanesulfonic acid (5.5 ml, 62 mmol). Stir 30 min and add <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (3.00 g, 13.8 mmol). Heat at reflux 2 h, allow to cool, concentrate, and partition with EtOAc and satd. NaHCO3. Dry (MgSO4), concentrate, and chromatograph on silica to obtain the oxazole as a yellow oil.

Reference： [1]Patent: US2007/66620,2007,A1 .Location in patent: Page/Page column 16

34
[ 1007-15-4 ]
[ 77287-34-4 ]
[ 929884-64-0 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: To <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (3.50 g, 16.1 mmol) in formamide (10 ml) add bromine (0.83 ml, 16.1 mmol). Heat at 75 C. 2 h, then 135 C. 5 h. Allow to cool and partition with EtOAc and satd. NaHCO3. Dry (MgSO4), concentrate, and chromatograph on silica to obtain the oxazole as a yellow oil.

Reference： [1]Patent: US2007/66620,2007,A1 .Location in patent: Page/Page column 16

35
[ 1007-15-4 ]
[ 109-94-4 ]
[ 929885-03-0 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: To <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (3.50 g, 16.1 mmol) in THF (100 ml) add KO-tBu (2.53 g, 16.1 mmol) and ethyl formate (3.9 ml, 48 mmol). Stir 18 h and add 1N NaOH (150 ml). Wash with ether and acidify with conc. HCl to pH1. Extract with ether, dry (MgSO4), and concentrate to obtain the crude formyl compound.

Reference： [1]Patent: US2007/66620,2007,A1 .Location in patent: Page/Page column 25-26

36
[ 403-42-9 ]
[ 176548-69-9 ]
[ 1007-15-4 ]

Yield	Reaction Conditions	Operation in experiment
28%; 42%		EXAMPLE A5(3,5-dibromo-4-fluorophenyl)-ethanone and (3-bromo-4-fluorophenyl)-ethanone69 g (0.5 mol) of p-fluoroacetophenone were added dropwise to 200.0 g (1.5 mol) of finely powdered aluminium chloride with stirring, during which time the mixture heated up to 70 C. It was kept at 75-80 C. for another 20 minutes and then 184 g (1.15 mol) of bromine were added at this temperature within 2.5 hours. Finally, the resulting mixture was heated to 90 C. for another 3 hours. After being cooled and decolorised the mixture was divided between water and tert.butylmethyl ether. Working up the organic phase yielded 130 g of a brownish-black oil which was separated into 2 fractions on silica gel using toluene as eluant: a) 41.2 g (28% of theoretical) of colourless crystals, m.p. 59-62 C. and Rf=0.53 (toluene), which were identified as 1-(3,5-dibromo-4-fluorophenyl)-1-ethanone by spectroscopy. IR (KBr):1685 (CO) cm-1 MS:M+ = 294/296/298 (Br2) b) 46.0 g (42% of theoretical) of colourless crystals, m.p. 52-55 C. and Rf=0.41 (toluene), which were identified as 1-(3-bromo-4-fluorophenyl)-1-ethanone by spectroscopy. IR (KBr):1682 (CO) cm-1 MS:M+ = 216/218 (Br)

Reference： [1]Patent: US7230001,2007,B1 .Location in patent: Page/Page column 67-68

37
[ 1007-15-4 ]
[ 765916-94-7 ]

Yield	Reaction Conditions	Operation in experiment
	With selenium(IV) oxide; In 1,4-dioxane; diethyl ether; 2-Methylpentane; water;	EXAMPLE 8 5-(3-Bromo-4-fluorophenyl)-3-(2.4-difluorophenvl)-[1,2,4]triazine To 3-bromo-4-fluoroacetophenone (11.0 g) in 1,4-dioxane (160 ml) and water (15 ml) was added selenium dioxide (8.8 g). The mixture was heated at reflux for 10 h, cooled to room temperature, and the solvent then removed at reduced pressure. The residue was suspended in 50% diethyl ether in isohexane, and residual solid removed by filtration. The filtrate was dried over Na2SO4, and solvent then evaporated to give (3-bromo-4-fluorophenyl)oxoacetaldehyde as a yellow oil, which was used without further purification in the next step.

Reference： [1]Patent: US2004/192692,2004,A1

38
[ 1007-15-4 ]
[ 128796-39-4 ]
[ 874183-31-0 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃; for 18h;	3-Bromo-4-fluoroacetophenone (4.34g, 20 mmol) in dioxan (60ml) was treated with 4- trifluoromethylphenyl boronic acid (5.3g, 30mmol) and saturated sodium carbonate solution (30ml). After degassing with nitrogen , [l,l'-diphenylphosphino)ferrocene]- dichloropalladium(?), (816mg, lmmol) was added and the mixture degassed. The reaction was heated for 18 hours at 1000C, cooled to room temperature and water (50ml) added. The reaction mixture was extracted with ethyl acetate (4x50ml). The combined organics were dried over sodium sulphate, filtered and evaporated. Purification by flash chromatography on silica using 5% ethyl acetate in isohexane as eluant yielded 3- (4- (trifluoromethyl)phenyl-4-fluoroacetophenone (4.6g, 81%). This intermediate (847mg, 3mmol), potassium carbonate (415mg, 3mmol) and phenylpiperazine (383mg, 3.6mmol) in DMSO (3ml) were heated at 95C for 18 hours. The mixture was partitioned between water (15ml) and ethyl acetate (35ml). The organic layer was washed with brine (15ml), dried over sodium sulphate, filtered and evaporated. Purification by flash chromatography on silica using 10% ethyl acetate in isohexane as eluant yielded 3- (4- (trifluoromethyl)phenyl)-4- ( 1 - (4-phenyl)piperazinyl) - acetophenone (160mg, 13%). This compound (141m, 0.33mmol) was treated with sulphur (27mg, 0.83mmol) and morpholine (174uL, 2mmol) and the mixture heated at 1700C for 10 minutes using an Emrys Optimiser microwave synthesizer, then cooled to room temperature. The crude mixture was purified by flash chromatography on silica using 20% ethyl acetate in isohexane as eluant to give 4-{2-[6-(4-phenylpiperazin- l-yl)-4'-(trifluoromethyl)biphenyl-3- yl]ethaneMoyl}morpholine. (142mg, 81%). This thioamide (50mg, 0.095mmol) in ethanol (15ml) was treated with 4N sodium hydroxide and heated at reflux overnight. The solvent was removed and the residue was treated with 2N hydrochloric acid. Water (5ml) was added and the aqueous was extracted using dichloromethane containing methanol. The combined organics were evaporated and purified by mass- triggered HPLC to give the title compound (7.5 mg, 14%) as the trifluoroacetate salt, MS: 441 (ES (M+l)). 1H NMR (500 MHz, CDCl3) delta 3.25 (4H, m, br.), 3.39 (4H, m, br.), 3.66 (2H, s), 7.12 - 7.52 (8H, m), 7.68 - 7.73 (4H, m) ppm.

Reference： [1]Patent: WO2006/8558,2006,A1 .Location in patent: Page/Page column 32-33

39
[ 1007-15-4 ]
[ 30766-22-4 ]
[ 1100767-32-5 ]

Yield	Reaction Conditions	Operation in experiment
28%	With 18-crown-6 ether; 40% potassium fluoride/alumina; In acetonitrile; for 72h;Heating / reflux;	Methyl-5-hydroxynicotinate (1.0 g, 6.53 mmol), <strong>[1007-15-4]3'-bromo-4'-fluoroacetophenone</strong> (1.42 g, 6.53 mmol), 18-crown-6 (155.3 mg, 0.59 mmol) and potassium fluoride (40 wt. % on alumina, 996 mg, 6.86 mmol) were dissolved in ACN (10 ml_). The reaction was refluxed for three days. After cooling the mixture was quenched with 2N aqueous potassium carbonate solution, extracted with ether, dried with sodium sulphate, filtered, evaporated and purified by silica gel chromatography (ethyl acetate: n-heptane 1 :4). 635 mg (yield: 28%) of the pure compound was obtained. LC/MS (method D) (M+H)+: 351

Reference： [1]Patent: WO2009/7015,2009,A1 .Location in patent: Page/Page column 39-40

40
[ 1007-15-4 ]
[ 96013-78-4 ]
[ 1100767-49-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With 18-crown-6 ether; 40% potassium fluoride/alumina; In acetonitrile; at 120℃; for 0.5h;microwave;	The product derived from step 1 (1.00 g, 4.19 mmol), 3'-bromo-4'-fluoroaceto-phenone(910 mg, 4.19 mmol), 18-crown-6 (99.8 mg, 0.38 mmol) and potassium fluoride (40 wt.% on alumina, 640 mg, 4.40 mmol) were dissolved in ACN (5 ml_). The reaction was stirred for 30 min at 120 0C in the microwave. The mixture was quenched with water, extracted with ethyl acetate, dried over sodium sulphate, filtered, evaporated and purified by silica gel chromatography (ethyl acetate:n-heptane 1 :10). Finally 1.35 g(yield: 74%) of the title compound was obtained.LC/MS (method D) (M+H)+: 436

Reference： [1]Patent: WO2009/7015,2009,A1 .Location in patent: Page/Page column 43

41
[ 1007-15-4 ]
[ 130336-16-2 ]
[ 1125812-41-0 ]

Yield	Reaction Conditions	Operation in experiment
39%		Lithium diisopropylamide (Aldrich Chemical Company, 2M in tetrahydrofuran/ ethylbenzene 10.18 mL, 20.36 mmol) was added to tetrahydrofuran (8 mL) at -78 0C. A solution of l-(3-bromo-4-fluorophenyl)ethanone (4.01 g, 18.47 mmol) in tetrahydrofuran (8 mL) was added dropwise to the mixture. When the addition was complete the mixture was stirred at -78 0C for 30 min. Then a solution of l-(3,5-dichlorophenyl)-2,2,2- trifluoroethanone (4.50 g, 18.52 mmol) in tetrahydrofuran (8 mL) was added dropwise to the mixture so the temperature of the reaction mixture did not exceed -60 0C. After the addition was complete the mixture was stirred at -78 0C for 60 min. The mixture was allowed to warm to 0 0C and then poured into IN hydrochloric acid (100 mL). The mixture was extracted with ethyl acetate (2 x 100 mL), and the combined extracts were dried and evaporated. Chromatography of the residue on silica gel (eluted with 1 :4 ethyl acetate/hexanes) gave the title product as a white solid (3.32 g, 39% yield) melting at 134- 135 0C (after crystallization from ethyl acetate/hexanes). IR (nujol) 3466, 1679, 1591, 1571, 1346, 1252, 1236, 1213, 1185, 1159, 1142, 1054, 825, 803 cm-1.1H NMR (CDCl3), delta 8.16 (dd, J=6.5,2.2 Hz, IH), 7.94-7.89 (m, IH), 7.48 (s, 2H), 7.36 (s, IH), 7.26 (t, J=8.2 Hz, IH), 5.55 (s, IH), 3.80 (1/2 ABq, J=17.5 Hz, IH), 3.65 (1/2 ABq, J=17.5 Hz, IH).

Reference： [1]Patent: WO2009/25983,2009,A2 .Location in patent: Page/Page column 39

42
[ 1007-15-4 ]
[ 93-97-0 ]
[ 934826-17-2 ]

Yield	Reaction Conditions	Operation in experiment
24%	With sodium hydride; In tetrahydrofuran; at 20℃; for 2h;	To a solution of <strong>[1007-15-4]1-(3-bromo-4-fluorophenyl)ethanone</strong> (3.0 g, 14 mmol) in tetrahydrofuran (15 mL) was added sodium hydride (1.6 g, 42 mmol), followed by benzoic anhydride (3.1 g, 14 mmol) and the resultant solution was stirred at room temperature for 2 hours. The solution was quenched with water and acidified to pH 5 using concentrated hydrochloric acid, then partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted (2×50 mL ethyl acetate). The combined organic layers were dried (sodium sulfate), filtered and concentrated in vacuo. Column chromatography (silica gel, 10:1 hexanes/ethyl acetate) gave 1.08 g (24% yield) of 1-(3-bromo-4-fluorophenyl)-3-phenylpropane-1,3-dione. 1H NMR (400 MHz, CDCl3): 8.19 (d, 1H), 7.97 (d, 2H), 7.90 (m, 1H), 7.57 (t, 1H), 7.49 (t, 2H), 7.21 (t, 1H), 6.75 (s, 1H).

Reference： [1]Patent: US2009/215803,2009,A1 .Location in patent: Page/Page column 35

43
[ 1007-15-4 ]
[ 100-58-3 ]
C₁₄H₁₂BrFO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		2-Bromo-1-fluoro-4-(1-phenyl-vinyl)-benzene A solution of <strong>[1007-15-4]4-fluoro-3-bromoacetophenone</strong> (3.0 g, 13.8 mmol, 1 eq) in 25 mL of dry tetrahydrofuran was added dropwise to a solution of phenyl magnesium bromide (15 mL of a 1.0 M solution in tetrahydrofuran, 15.2 mmol, 1.1 eq) in 40 mL of dry tetrahydrofuran at 0 C. and under an inert atmosphere. The reaction was stirred for 4 h while warming to room temperature. It was then was examined by TLC (cyclohexane/ethyl acetate 2%) which showed complete consumption of starting material. The solution was quenched with water, until gas evolution ceased, and 1 N hydrochloric acid was added to reach pH=5. Diethyl ether (20 mL) was added and the two phases were separated; the organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crude (tertiary alcohol) and a catalytic amount of p-toluene sulfonic acid were dissolved in 100 mL of toluene and the mixture was heated to reflux for 3 h (using a Dean-Stark apparatus). The reaction mixture was examined by TLC (cyclohexane/ethyl acetate 3%) which showed complete consumption of starting material. The solvent was evaporated under reduced pressure and the crude was purified by flash chromatography eluding with neat cyclohexane. 2.1 g of desired product was obtained as a liquid (yield: 55%). Mass (calculated) C14H10BrF [277] MH+ not observed LC Rt=3.03, 94% (5 min method) 1H-NMR (CDCl3): 5.43 (d, 1H), 5.48 (d, 1H), 7.08 (t, 1H), 7.25 (m, 1H), 7.31 (m, 5H), 7.54 (m, 1H)

Reference： [1]Patent: US2009/209529,2009,A1 .Location in patent: Page/Page column 9-10

44
[ 14804-31-0 ]
[ 1007-15-4 ]
C₁₆H₁₆BrFO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		4-[1-(3-Bromo-4-fluoro-phenyl)-vinyl]-1-methoxy-2-methyl-benzene 8 mL of a solution of 4-bromo-2-methylanisole (5.22 g, 26 mmol, 1.1 eq) in 40 mL of dry diethyl ether was added dropwise to a mixture of magnesium turnings (700 mg, 28.8 mmol, 1.2 eq) in 5 mL of dry diethyl ether under an inert atmosphere. A drop of bromine was added to initiate the reaction and gas evolution was observed. The remaining solution of 4-bromo-2-methylanisole (32 mL) was added and the reaction was stirred for 4 h at room temperature. The solution was then cooled to 0 C. and a solution of <strong>[1007-15-4]4-fluoro-3-bromoacetophenone</strong> in 40 mL of dry diethyl ether was added; the mixture was stirred while warming to room temperature for 2 h. The solution was examined by TLC (cyclohexane/ethyl acetate 6%) which showed consumption of starting material. The solution was quenched with water, until gas evolution ceased, and then 1N HCl was added to reach a pH=5. The two phases formed were separated; the organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crude (tertiary alcohol) and a catalytic amount of p-toluene sulfonic acid were dissolved in 100 mL toluene (Dean-Stark apparatus) and the mixture was heated to reflux for 3 h. The solution was examined by TLC (cyclohexane/ethyl acetate 6%) which showed consumption of starting material but many side products formed. Solvent was evaporated under reduced pressure and the crude residue was purified by flash chromatography eluding with a gradient (cyclohexane/ethyl acetate 0-4%). 1.65 g of product was obtained as liquid (20%). Mass (calculated) C16H14BrFO [321] M-H+ not observed LC Rt=3.15, (5 min method) 1H-NMR (CDCl3): 2.21 (s, 3H); 3.85 (s, 3H); 5.29 (s, 1H), 5.38 (s, 1H), 6.79 (m, 1H), 6.84 (m, 1H), 7.09 (m, 2H), 7.24 (m, 1H); 7.55 (m, 1H) 90%

Reference： [1]Patent: US2009/209529,2009,A1 .Location in patent: Page/Page column 12

45
[ 179636-73-8 ]
[ 1007-15-4 ]
C₂₀H₂₆BrFO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		{4-[1-(3-Bromo-4-fluoro-phenyl)-vinyl]-phenoxy}-tert-butyl-dimethyl-silane To a mixture of magnesium turnings (1.5 g, 0.06 mol, 1.2 eq) in dry tetrahydrofuran (10 mL), was added a portion (1/5) of (4-bromo-2-methyl-phenoxy)-tert-butyl-dimethyl-silane (16.0 g, 0.05 mol, 1.1 eq) in dry tetrahydrofuran (50 mL) and 1,2-dibromoethane (0.5 mL). The resulting solution was refluxed and the other (4/5) portion of the above solution was added and the resulting solution was refluxed for 2 h. After cooled at 0 C. a solution of 3-bromo-4-fluoroacetophenone (11.5 g, 0.05 mol, 1 eq) in dry tetrahydrofuran (40 mL) was added dropwise and the reaction was stirred for 3 h at room temperature. The mixture was quenched with saturated ammonium chloride solution (20 mL). The aqueous phase was extracted with dichloromethane (3*20 mL), dried (sodium sulfate) and the solvent removed in vacuo. The crude latter was dissolved in toluene (200 mL) and a catalytic amount (30 mg) of p-toluenesulfonic acid was added and refluxed for 3 h. The solvent was removed and the residue was purified by column chromatography (cyclohexane) to afford the title compound as a colourless oil (18.5 g, 39%). Mass (calculated) C20H24BrFOSi [407]; (found) [M+H+]=423 LC Rt=3.44 min (5 min method) 1H-NMR (CDCl3): 0.0 (s, 6H), 0.80 (s, 9H), 1.99 (s, 3H), 5.05 (d, 1H), 5.16 (d, 1H), 6.50 (m, 1H), 6.76 (m, 1H), 6.86 (m, 2H), 7.01 (m, 1H), 7.32 (m, 1H)

Reference： [1]Patent: US2009/209529,2009,A1 .Location in patent: Page/Page column 27

46
[ 50638-47-6 ]
[ 1007-15-4 ]
C₁₅H₁₃BrClFO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1-Bromo-3-[1-(4-methoxy-3-chlorophenyl)-vinyl]-6-fluorobenzene A solution of n-butyllithium (1.6 M solution in hexane, 20 mL, 1.1 eq) was added dropwise to a solution of <strong>[50638-47-6]4-bromo-2-chloro-1-methoxy-benzene</strong> (6 g, 27 mmol, 1 eq) in tetrahydrofuran (25 mL) at -78 C. After stirring 30 min 3-bromo-4-fluoroacetophenone (5.8 g, 27 mmol, 1 eq) in tetrahydrofuran (25 mL) was added dropwise. The mixture was allowed to warm up to room temperature and stirred for 2 h, then treated with water (10 mL), extracted with ethyl acetate, dried (sodium sulfate) and concentrated in vacuo. The crude was dissolved in acetic acid (80 mL) and concentrated sulfuric acid (17 mL) was added. The mixture was warmed to 75 C. for 30 min, cooled at room temperature and neutralized with 1 N NaOH. The aqueous phase was extracted with dichloromethane (3*100 mL), dried (sodium sulfate) the solvent was removed under reduced pressure. The residue was purified by column chromatography (cyclohexane) to afford the title compound as a colourless oil (3.2 g, 36%); Mass (calculated) C15H11BrClFO [341]; (found) [M+H+]=342 LC Rt=3.05 min (5 min method) 1H-NMR (CDCl3): 3.90 (s, 3H), 5.35 (d, 2H), 6.88 (m, 1H), 7.06-7.26 (m, 4H), 7.50 (m, 1H)

Reference： [1]Patent: US2009/209529,2009,A1 .Location in patent: Page/Page column 24

47
[ 1007-15-4 ]
[ 540-63-6 ]
[ 1262048-09-8 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 9996 - 10001

48
[ 1338926-79-6 ]
[ 1007-15-4 ]
[ 1338926-74-1 ]

Yield	Reaction Conditions	Operation in experiment
		Synthesis of example A-i; Under argon atmosphere, to a tetrahydrofuran solution (5 ml) of 0.07 g 3-bromo-4-fluoroacetophenone, 0.16 ml 2.0 M tetrahydrofuran solution of lithium diisopropylamide was added at -75C. After stirring for 30 minutes, the reaction mixture was added with 0.1 g 1 ,2,3-trichloro-5- (3,3,3-trifluoro-l-nitroprop-l-en-2-yl) benzene, and the mixture was stirred for 5 hours. A saturated aqueous solution of ammonium chloride was added to the mixture and extracted with ethyl acetate. The oganic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 0.19 g (83% purity)1 -(3-bromo-4-fluorophenyl)-4,4,4-trifluoro-3-(nitromethyl)-3-(3,4,5-trichlorophenyl)-butan- 1 -one. -NMR (CDC13) delta: 4.01 (2H, dd), 5.49 (2H, dd), 7.08-7.42 (3H, m), 7.92-7.95 (1H, m), 8.18-8.21 (1H, m).

Reference： [1]Patent: WO2011/128299,2011,A1 .Location in patent: Page/Page column 41; 93-94

49
[ 1007-15-4 ]
[ 1246248-64-5 ]

Reference： [1]Patent: EP2409977,2012,A1

50
[ 1007-15-4 ]
[ 1246248-65-6 ]

Reference： [1]Patent: EP2409977,2012,A1

51
[ 1007-15-4 ]
[ 1246248-67-8 ]

Reference： [1]Patent: EP2409977,2012,A1

52
[ 1007-15-4 ]
[ 1246248-68-9 ]

Reference： [1]Patent: EP2409977,2012,A1

53
[ 1007-15-4 ]
[ 1246248-66-7 ]

Reference： [1]Patent: EP2409977,2012,A1

54
[ 1007-15-4 ]
[ 676-58-4 ]
[ 1194045-07-2 ]

Yield	Reaction Conditions	Operation in experiment
42%		1-(3-Bromo-4-fluorophenyl)ethanone (5.0 g, 23.0 mmol) was dissolved in toluene (100 mL), a 3.0 M methylmagnesium chloride-tetrahydrofuran solution (11.5 mL, 34.6 mmol) was added dropwise with stirring under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. Subsequently, acetic acid (1 mL) was added with stirring under ice cooling, and the mixture was stirred with heating to reflux for 4 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added with stirring under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 50:1, v/v) to give the title compound (2.06 g; yield, 42%) as a colorless oily substance. 1H HMR (CDCl3, 500 MHz) : delta 2.1 (3H, s), 5.1 (1H, s), 5.3 (1H, s), 7.0-7.1 (1H, m), 7.3-7.4 (1H, m), 7.6-7.7 (1H, m).

Reference： [1]Patent: EP2409977,2012,A1 .Location in patent: Page/Page column 136

55
[ 1007-15-4 ]
[ 1338926-74-1 ]

Reference： [1]Patent: WO2012/34957,2012,A1

56
[ 1007-15-4 ]
[ 1364921-44-7 ]

Reference： [1]Patent: WO2012/34957,2012,A1

57
[ 1007-15-4 ]
[ 1364921-78-7 ]

Reference： [1]Patent: WO2012/34957,2012,A1

58
[ 1007-15-4 ]
[ 1364921-33-4 ]

Reference： [1]Patent: WO2012/34957,2012,A1

59
[ 1007-15-4 ]
1-(3,4,5-trichloro-phenyl)-2,2,2-trifluoro-ethanone [ No CAS ]
[ 1364932-09-1 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hydride; In tetrahydrofuran; for 8h;Reflux;	Lithium hydride (0.1 g) was added to tetrahydrofuran solution (50 mL) of 2,2,2-trifluoro-l-(3,4,5- trichlorophenyl)ethanone (4.0 g) and l-(3-bromo-4-fluorophenyl) ethanone (1.5 g) followed by reflux under heating for 8 hours. The mixture was diluted with t-butyl methyl ether and washed with sodium hydrogen carbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate / hexane) to obtain l-(3-bromo-4-fluorophenyl)-4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-2-en- 1 -one (2.6g) .1H-NMR(CDCl3)5:7.23-7.34(4H,m), 7.79-7.82(lH,m), 8.03-8.08(lH,m)

Reference： [1]Patent: WO2012/34957,2012,A1 .Location in patent: Page/Page column 55-56

60
[ 1007-15-4 ]
[ 17997-47-6 ]
[ 1369355-13-4 ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 69 - 73

61
[ 1007-15-4 ]
[ 1421030-13-8 ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 69 - 73

62
[ 1007-15-4 ]
[ 1421029-98-2 ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 69 - 73

63
[ 1007-15-4 ]
[ 1421029-94-8 ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 69 - 73

64
[ 1007-15-4 ]
C₃₁H₂₉FN₂OPt [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 69 - 73

65
[ 1007-15-4 ]
1-(5-bromo-2,4-difluorophenyl)ethanone [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 69 - 73

66
[ 1007-15-4 ]
[ 1413285-64-9 ]

Reference： [1]Patent: WO2012/156400,2012,A1
[2]Patent: WO2014/79941,2014,A1

67
[ 1007-15-4 ]
(5R)-3-(3-bromo-4-tert-butylsulfanylphenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazole [ No CAS ]
[ 1413285-65-0 ]

Reference： [1]Patent: WO2012/156400,2012,A1
[2]Patent: WO2014/79941,2014,A1
[3]Patent: WO2014/79937,2014,A1

68
[ 1007-15-4 ]
[ 75-66-1 ]
[ 1341083-44-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 4h;	In a mechanically stirred reactor was charged dimethylformamide (350 mL), l-(4-fluoro-3-bromo- phenyl)-ethanone (30 g), potassium carbonate (29 g) followed by tert-butylthiol (18.7 g). The resulting suspension was heated to 50C for 4 hours. The mixture was then cooled to room temperature and poured in brine (1 L), and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with brine and dried over MgS04. The solvents were removed to leave the desired compound (40 g). LCMS (Method E) RT 1.11 min. [M+H]+ 277-279. lB NMR (400 MHz, CDC13) 1.40 (s, 9H), 2.59 (s, 3H), 7.70 (d, 1H), 7.71 (dd, 1H), 8.19 (d, 1H).
40 g	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 4h;	Step A: l-(3-bromo-4-tert-butylsulfanyl-phenyl)ethanone In a mechanically stirred reactor was charged dimethylformamide (350 mL), l-(4-fluoro-3-bromo- phenyl)-ethanone (30 g), potassium carbonate (29 g) followed by tert-butylthiol (18.7 g). The resulting suspension was heated to 50C for 4 hours. The mixture was then cooled to room temperature and poured 5 in brine (1 L), and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with brine and dried over MgSO i. The solvents were removed to leave the desired compound (40 g). LCMS (Method A) RT 1.11 min. [M+H]+ 277-279. lB NMR (400 MHz, CDC13) 1.40 (s, 9H), 2.59 (s, 3H), 7.70 (d, 1H), 7.71 (dd, 1H), 8.19 (d, 1H).
40 g	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 4h;	In a mechanically stirred reactor was charged dimethylformamide (350 mL), l-(4-fluoro-3-bromo- phenyl)-ethanone (30 g), potassium carbonate (29 g) followed by tert-butylthiol (18.7 g). The resulting suspension was heated to 50C for 4 hours. The mixture was then cooled to room temperature and poured 5 in brine (1 L), and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with brine and dried over MgSO i. The solvents were removed to leave the desired compound (40 g). LCMS (Method A) RT 1.11 min. [M+H]+ 277-279. lB NMR (400 MHz, CDC13) 1.40 (s, 9H), 2.59 (s, 3H), 7.70 (d, 1H), 7.71 (dd, 1H), 8.19 (d, 1H).

Reference： [1]Patent: WO2012/156400,2012,A1 .Location in patent: Page/Page column 207
[2]Patent: WO2014/79941,2014,A1 .Location in patent: Page/Page column 115-116
[3]Patent: WO2014/79937,2014,A1 .Location in patent: Page/Page column 106; 107

69
[ 1007-15-4 ]
[ 1415829-46-7 ]

Reference： [1]Patent: US2012/316172,2012,A1
[2]Patent: WO2012/168260,2012,A1

70
[ 1007-15-4 ]
[ 1354895-73-0 ]

Reference： [1]Patent: US2012/316172,2012,A1
[2]Patent: WO2012/168260,2012,A1

71
[ 1007-15-4 ]
[ 1415829-44-5 ]

Reference： [1]Patent: US2012/316172,2012,A1
[2]Patent: WO2012/168260,2012,A1

72
[ 1007-15-4 ]
[ 95-92-1 ]
lithium (Z)-4-(3-bromo-4-fluorophenyl)-1-ethoxy-1,4-dioxobut-2-en-2-olate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.9%		Preparation of 5-(3-Cyano-4-fluoro-phenyl)-1H-pyrazole-3-carboxylic acida) Lithium (Z)-4-(3-bromo-4-fluorophenyl)-1-ethoxy-1,4-dioxobut-2-en-2-olate: to a magnetically stirred solution of LiHMDS in THF 1M (9.22 ml, 9.22 mmol, Eq: 1) was added Et2O (31.2 ml) at -78 C. to give a yellow solution. To this mixture was added a solution of <strong>[1007-15-4]1-(3-bromo-4-fluorophenyl)ethanone</strong> (2 g, 9.22 mmol, Eq: 1.00) in Et2O (15.6 ml) dropwise under argon atmosphere. The mixture was then stirred at the same temperature for an additional period of 45 min. Diethyl oxalate (1.41 g, 1.31 ml, 9.68 mmol, Eq: 1.05) was then added dropwise. The reaction mixture was allowed to warm to rt and stirred for another 2 days. The precipitate formed was collected by filtration, washed with diethyl ether, and dried under vacuum to afford the desired lithium salt as a light-yellow solid (2.677 g, 89.9%).
89.9%		a) Lithium (Z)-4-(3-bromo-4-fluorophenyl)-l-ethoxy-l,4-dioxobut-2-en-2-olate: to amagnetically stirred solution of LiHMDS in THF 1M (9.22 ml, 9.22 mmol, Eq: 1) was added Et20 (31.2 ml) at -78C to give a yellow solution. To this mixture was added a solution of l-(3-bromo-4-fluorophenyl)ethanone (2 g, 9.22 mmol, Eq: 1.00) in Et20 (15.6 ml) dropwise under argon atmosphere. The mixture was then stirred at the same temperature for an additional period of 45 min. Diethyl oxalate (1.41 g, 1.31 ml, 9.68 mmol, Eq: 1.05) was then added dropwise. The reaction mixture was allowed to warm to rt and stirred for another 2 days. The precipitate formed was collected by filtration, washed with diethyl ether, and dried under vacuum to afford the desired lithium salt as a light-yellow solid (2.677g, 89.9%).

Reference： [1]Patent: US2012/316172,2012,A1 .Location in patent: Page/Page column 19
[2]Patent: WO2012/168260,2012,A1 .Location in patent: Page/Page column 37

73
[ 1007-15-4 ]
2-acetyldibenzo[b,d]thiophene-5-oxide [ No CAS ]