Name: 529-35-1|5,6,7,8-Tetrahydro-1-naphthol|98%
Brand: Ambeed
SKU: A292753
Price: 5.0 USD
Availability: InStock
Rating: 95 (40 reviews)

1
[ 90-15-3 ]
[ 529-35-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With palladium on activated charcoal; hydrogen In ethanol at 50℃; for 8h; Autoclave;	Step i. Synthesis of compound 20 To a solution of 1-naphthol 19 (20.0 g, 0.139 mol) in EtOH (150 mL) was added Pd/C (4.0 g, wt. 10%). The reaction mixture was stirred at 50 °C under 80 atm H2 in an autoclave for 8 h. The reaction mixture was cooled down to room temperature, filtered and concentrated via rotary evaporator under reduced pressure. The residue S-3 was purified by flash chromatography on silica gel (petroleum ether / ethyl acetate = 20:1) to give the compound 20 (19.5 g, 95% yield) as a white solid.1 20: White solid; IR (KBr) 3290, 2931, 2859, 1584, 1462, 1249, 770 cm-1; 1H NMR (400 MHz,CDCl3) δ 7.06 (t, J = 7.8 Hz, 1H), 6.77 (d, J = 7.6 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H), 5.26 (br, 1H), 2.83 (t, J = 5.8 Hz, 2H), 2.71 (t, J = 6.0 Hz, 2H), 1.93-1.87 (m, 2H), 1.87-1.81 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 153.4, 139.0, 126.0, 123.6, 121.7, 111.9, 29.7, 22.9, 22.8, 22.8.
93%	With Raney Ni-Al In potassium hydroxide; water at 90℃; for 3.5h;
80%	With nickel-aluminum alloy; water; sodium hydroxide at 90 - 95℃; for 9h;	4.1 (1)Preparation of tetrahydronaphthol (intermediate VI): 2 g of 1-naphthol was dissolved in 40 ml of 7.8% aqueous sodium hydroxide solution.Heating the reaction system to 90 ° C ~ 95 ° C,Control the temperature and slowly add 13 grams of nickel-aluminum alloy for 9 hours.The reaction solution is filtered while hot, after the system is cooled to room temperature,Add appropriate amount of dilute hydrochloric acid, adjust the pH to 3 to 4, then extract it with ethyl acetate three times, dry over anhydrous magnesium sulfate, filter, and concentrate.The residue was purified by column chromatography eluting elutThe yield was 80%.

74%	With potassium hydroxide; Raney Ni-Al alloy In water at 90℃; for 2h;
	With lithium; methylamine
	With hydrogenchloride; platinum at 70℃; Hydrogenation;
	With sodium hydroxide; aluminum nickel at 90℃;
	With ethanol; copper oxide-chromium oxide at 150 - 190℃; Hydrogenation;
	With 1,4-dioxane; nickel at 150 - 190℃; Hydrogenation;
	With 1,4-dioxane; copper oxide-chromium oxide at 150 - 190℃; Hydrogenation;
	With ammonia; sodium
	With pentan-1-ol; sodium
	With pentan-1-ol; sodium mehrfach behandeln;
	With ethanol; nickel at 150 - 190℃; Hydrogenation;
	With diethyl ether; ammonia; lithium weiteres Reagens: Aethanol; Hydrierung des Reaktionsprodukts an Palladium/Kohle in Aethylacetat;
	With potassium hydroxide at 90℃; for 2h;
	Multi-step reaction with 2 steps 1: alcohol; sodium; solvent naphtha 2: sodium; alcohol
	With hydrogen
	With ethanol; sodium
81.5 g	With nickel-aluminum alloy; sodium hydroxide at 70 - 95℃; for 14h;	2.1 Step (1): Preparation of 5,6,7,8-tetrahydro-1-naphthol Add in 2000ml reaction flask700ml 7.8% sodium hydroxide solution,When stirring and heating to 70°C, add 40g of 1-naphthol and continue heating to 90°C.Gradually add 190g of aluminum-nickel alloy gradually and keep it at 90-95°C.When the reaction was completed for 5 hours, 300 ml of 7.8% sodium hydroxide solution was added, and the aluminum-nickel alloy was added within 9 hours.After the reaction is completed, cool the material and filter the solid nickel in the reaction mixture. Wash the water, combine the filtrate, and stir.Acidification with 500 ml of hydrochloric acid precipitated an off-white solid, which was collected by filtration.It was washed with water and dried to obtain 81.5 g of 5,6,7,8-tetrahydro-1-naphthol wet material.37.6 g of 5,6,7,8-tetrahydro-1-naphthol was detected by HPLC with a yield of 91.5%.
	With sodium hydroxide; aluminum nickel at 90℃;

Reference： [1]Hou, Chengkang; Zhao, Guoqing; Xu, Dongfang; Zhao, Baoguo [Tetrahedron Letters, 2018, vol. 59, # 11, p. 1028 - 1033]
[2]Tsukinoki, Takehito; Kanda, Tadashige; Liu, Guo-Bin; Tsuzuki, Hirohisa; Tashiro, Masashi [Tetrahedron Letters, 2000, vol. 41, # 31, p. 5865 - 5868]
[3]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; Shanghai Institute of Materia Medica (in: CAS); EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN108997163, 2018, A Location in patent: Paragraph 0122; 0123; 0124
[4]Wang, Yang; Huang, Shaoxu; Xia, Peng [Synthetic Communications, 2005, vol. 35, # 24, p. 3141 - 3156]
[5]Benkeser et al. [Journal of the American Chemical Society, 1958, vol. 80, p. 6573,6576][Journal of Organic Chemistry, 1959, vol. 24, p. 854]
[6]Brown; Durand; Marvel [Journal of the American Chemical Society, 1936, vol. 58, p. 1594,1596]
[7]Papa; Schwenk; Breiger [Journal of Organic Chemistry, 1949, vol. 14, p. 366,369]
[8]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666]
[9]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666]
[10]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666]
[11]White; Morrison; Anderson [Journal of the American Chemical Society, 1924, vol. 46, p. 967]
[12]Bamberger; Bordt [Chemische Berichte, 1890, vol. 23, p. 217]
[13]Jacobson; Turnbull [Chemische Berichte, 1898, vol. 31, p. 898]
[14]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666]
[15]Gutsche; Peter [Journal of the American Chemical Society, 1955, vol. 77, p. 5971,5974][Organic Syntheses, 1963, vol. Coll. Vol. IV, p. 887]
[16]Wang, Yang; Huang, Shao-Xu; Xia, Peng; Xia, Yi; Yang, Zheng-Yu; Kilgore, Nicole; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 15, p. 4316 - 4319]
[17]Rowe; Levin [Journal of the Chemical Society, 1921, vol. 119, p. 2028][Journal of the Chemical Society, 1927, p. 531]
[18]Location in patent: body text Poon; Banerjee, Ajoy K.; Bedoya, Liadis; Laya, Manuel S.; Cabrera, Elvia V.; Albornoz, Karla M. [Synthetic Communications, 2009, vol. 39, # 18, p. 3369 - 3377]
[19]Current Patent Assignee: CITIZEN WATCH CO LTD - US2013/172558, 2013, A1 Location in patent: Paragraph 0116
[20]Current Patent Assignee: KPC PHARMACEUTICALS, INC. - CN105085505, 2018, B Location in patent: Paragraph 0057; 0066-0068
[21]Current Patent Assignee: MERCK & CO INC - US2475718, 1946, A

2
[ 90-15-3 ]
[ 529-35-1 ]
[ 529-33-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; copper oxide-chromium oxide at 180 - 190℃; Hydrogenation;
	With copper at 150℃; Hydrogenation;
	With 1,4-dioxane; copper oxide-chromium oxide at 180 - 190℃; Hydrogenation;

With nickel at 130℃; Hydrogenation;

Reference： [1]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666]
[2]Komatsu; Sugino; Hagiwara [Proceedings of the Imperial Academy (Tokyo), 1930, vol. 6, p. 194,196]
[3]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666]
[4]Brochet; Cornubert [Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1921, vol. 172, p. 1500][Bulletin de la Societe Chimique de France, 1922, vol. <4> 31, p. 1283] Schroeter; Thomas [Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1918, vol. 101, p. 266 Anm. 4]

3
[ 529-35-1 ]
[ 108-24-7 ]
[ 91028-13-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine for 2h; Reflux;	12.1 Step1: 5,6,7,8-tetrahydronaphthalen-1-ol (50.85 g, 340 mmol) was dissolved in acetic anhydride (500 ml) and triethylamine(56.8 ml, 408 mmol) was added to the reaction mixture. The whole was refluxed for 2h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude remaining liquid was dissolved into ethyl acetate (500mL) and the organic layer was washed several times with water and brine. The organic layer was then dried over Na2SO4, filtered, concentrated under reduced pressure to give a dark oil (65.4g; 91 % yield) LC: 4.94 min
89%	With pyridine; dmap at 20℃; Inert atmosphere;
	With sulfuric acid at 20℃;

Reference： [1]Current Patent Assignee: POXEL - EP2679591, 2014, A1 Location in patent: Paragraph 0082
[2]Guo, Weisi; Li, Ming; Li, Yufeng; Wang, Tao; Wen, Lirong; Zhang, Shanxue [Organic Letters, 2022, vol. 24, # 8, p. 1742 - 1746]
[3]MOMOSE; OHKURA [Pharmaceutical bulletin, 1956, vol. 4, # 3, p. 209 - 211]

4
[ 529-35-1 ]
[ 106-95-6 ]
[ 107203-35-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With caesium carbonate In N,N-dimethyl-formamide at 25℃; for 2h; Inert atmosphere;	5-(Allyloxy)-1,2,3,4-tetrahydronaphthalene (2) To a solution of 1 (1.06 g, 6.75 mmol) in anhydrous DMF (30 mL) underan argon atmosphere was added Cs2CO3 (4.40 g, 13.50 mmol), followed by addition of 3-bromoprop-1-ene (2.34 mL, 27.00 mmol). The mixture was stirred for 2 h at 25 °C and the progress of the reaction was monitored by TLC. Sat. aq NH4Cl (50 mL) was added to quench the reaction, then H2O (300 mL) was added to dilute the resultant mixture.The aqueous layer was extracted with EtOAc (3 × 100 mL) and the organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, and evaporated under reduced pressure. The crude product was purified by silica gel column (EtOAc-petroleum ether, 1:50 v/v) to afford 2.
	With methanol; sodium methylate
	With sodium; toluene at 70 - 80℃;

With potassium carbonate; acetone

Reference： [1]Yin, Hongli; Meng, Zhe; Liu, Bo [Synthesis, 2016, vol. 48, # 22, p. 3951 - 3956]
[2]Ssergijewsskaja; Gawrilowa [Zhurnal Obshchei Khimii, 1941, vol. 11, p. 1027,1037][Chem.Abstr., 1945, p. 4601]
[3]Ssergijewsskaja; Gawrilowa [Zhurnal Obshchei Khimii, 1941, vol. 11, p. 1027,1037][Chem.Abstr., 1945, p. 4601]
[4]Takahashi et al. [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1958, vol. 78, p. 907,910][Chem.Abstr., 1958, p. 20010]

5
[ 529-35-1 ]
[ 77-78-1 ]
[ 1008-19-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydroxide In tetrahydrofuran at 0 - 20℃; for 3h;	XV Preparation of Compound XV-b A solution of compound XV-a (100 g, 674 mmol) in dry THF (600 mL) was charged with dimethyl sulfate (102 g, 809 mmol) followed by NaOH (32.4 g, 809 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated to remove the solvent and diluted with water. The aqueous layer was extracted with ethyl acetate (2×500 mL). The combined organic extracts were dried over Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, 90:10 hexane/EtOAc) to afford compound XV-b (108 g, 98%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ7.05 (t, J=7.8 Hz, 1H), 6.69 (d, J=7.6 Hz, 1H), 6.64 (d, J=7.9 Hz, 1H), 3.80 (s, 3H), 2.74 (t, J=6.2 Hz, 2H), 2.64 (t, J=6.2 Hz, 2H), 1.81-1.71 (m, 4H).
98%	With sodium hydroxide In tetrahydrofuran at 0 - 20℃; for 3h;	XV-b Preparation of Compound XV-b A solution of compound XV-a (100 g, 674 mmol) in dry THF (600 ml_) was charged with dimethyl sulfate (102 g, 809 mmol) followed by NaOH (32.4g, 809 mmol) at 0 °C. The resulting reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated to remove the solvent and diluted with water. The aqueous layer was extracted with ethyl acetate (2 x 500 ml_). The combined organic extracts were dried over Na2S04 and concentrated. The residue was purified by column chromatography (silica gel, 90:10 hexane/EtOAc) to afford compound XV-b (108 g, 98%) as a colorless oil. 1 H NMR (400 MHz, CDCI3): 57.05 (t, J = 7.8 Hz, 1 H), 6.69 (d, J = 7.6 Hz, 1 H), 6.64 (d, J = 7.9 Hz, 1 H), 3.80 (s, 3H), 2.74 (t, J = 6.2 Hz, 2H), 2.64 (t, J = 6.2 Hz, 2H), 1 .81-1 .71 (m, 4H).
90%	With sodium hydroxide at 0 - 20℃; for 2h;	16 Preparation of Compound 105; A solution of 104 (100 g, 0.675 mmol) in dry THF (800 mL) was charged with NaOH (32.0 mg, 0.809 mmol) and dimethylsulfate (102 g, 0.809 mmol) dropwise at 0° C. The reaction mixture was stirred for 2 h at room temperature. THF was removed under reduced pressure, and the mixture was partitioned between CH2Cl2 (1.0 L) and water (1.0 L). The aqueous layer was separated and extracted with CH2Cl2 (2×1.0 L). The combined organic extracts were dried over Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, 100% CH2Cl2) to afford compound 105 (108.0 g, 90%) as a yellow liquid: 1H NMR (400 MHz, DMSO-d6): δ 7.06 (t, J=7.85 Hz, 1H), 6.71 (d, J=7.25, 1H), 6.64 (t, J=7.7 Hz, 1H), 3.80 (s, 3H), 2.74 (t, J=2.75 Hz, 2H), 2.65 (t, J=2.65 Hz, 2H), 1.81-1.71 (m, 4H).

90%	With potassium carbonate In acetone Reflux;	S.3.1 Step 1: 5-Methoxytetralin Step 1: 5-MethoxytetralinA mixture of tetralin-5-ol (50 g), (CH3)2504 (400 g) and K2C03 (100 g) in acetone (1 L)was stirred at reflux overnight. Then, the mixture was concentrated. The residue wasdissolved in CH2CI2 and washed with water, dried (Na2504), filtered and concentratedto give a residue, which was purified by flash chromatography on silica gel (petroleumether I ethyl acetate) to afford the product (50 g, 90%).1H NMR (400 MHz, CDCI3): 7.12 (m, 1H), 6.81-6.70 (m, 2H), 3.86 (s, 3H), 2.81 (m,2H), 2.71 (m, 2H), 1.91-1.77 (m, 4H).
88%	With potassium carbonate In acetone for 15h; Reflux;	S.3.1 Step 1: 5-Methoxytetralin Step 1: 5-Methoxytetralin To a mixture of tetralin-5-ol (32 g) and K2003 (64 g) in acetone (600 mL) was added (CH3)2S04 (60 g), and the mixture was stirred at reflux for 15 h. Then, the mixture was filtered and concentrated. The crude product was purified by flash chromatography onsilica gel (petroleum ether I ethyl acetate) to afford the product (34 g, 88%).1H NMR (400 MHz, CDCI3): 7.12 (m, 1H), 6.81-6.70 (m, 2H), 3.86 (s, 3H), 2.81 (m,2H), 2.71 (m, 2H), 1.91-1.77 (m, 4H).
	With sodium hydroxide

Reference： [1]Current Patent Assignee: PARION SCIENCES INC - US2014/170244, 2014, A1 Location in patent: Paragraph 0451
[2]Current Patent Assignee: PARION SCIENCES INC - WO2014/99673, 2014, A1 Location in patent: Page/Page column 135; 137
[3]Current Patent Assignee: PARION SCIENCES INC - US2014/171447, 2014, A1 Location in patent: Paragraph 0371; 0372
[4]Current Patent Assignee: BASF SE - WO2014/206910, 2014, A1 Location in patent: Page/Page column 200
[5]Current Patent Assignee: BASF SE - WO2015/128358, 2015, A1 Location in patent: Page/Page column 151; 152
[6]Musser; Adkins [Journal of the American Chemical Society, 1938, vol. 60, p. 664,666] Bachmann; Ness [Journal of the American Chemical Society, 1942, vol. 64, p. 536,538]

6
[ 529-35-1 ]
[ 74-88-4 ]
[ 1008-19-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In acetone at 45℃; Heating / reflux;	2.a Example 2; Synthesis of 1,4-Disubstituted 5,6,7,8-Tetrahydro-naphthalene Derivatives; Preparation of 5-Methoxy-1,2,3,4-tetrahydro-naphthalene (Compound 40) The mixture of 5,6,7,8-tetrahydro-1-naphthol (5 g, 33.74 mmol), iodomethane (4.8 g, 33.74 mmol), anhydrous K2CO3 in 20 ml dry acetone was heated to reflux (45° C.) overnight. The solvent was removed and the residue was added to 50 ml water and extracted with 3*20 ml ethyl acetate. The organic layer was combined and washed with 30 ml brine, dried over anhydrous Na2SO4, filtered, and the solvent was removed to give the crude product. The crude product was purified by column chromatography to afford 5.47 g (100%) of 40. 1H-NMR (400 M, CD3COCD3) δ 1.73(m, 4H), 2.59(t, 2H), 2.70 (t, 2H), 3.78(s, 3H), 6.64(d, 1H), 6.77(d, 1H), 7.02(s, 1H). MS (EI) m/z: 162(M+).
100%	With potassium carbonate In acetone Reflux;	I.I-II.I-I Example I-IIPreparation of Compound 303 and 304General Procedure I-IThe mixture of 5,6,7,8-tetrahydronaphthalen-1-ol (IIa; 5 g, 33.74 mmol), CH3I (4.8 g, 33.74 mmol), and K2CO3 (35 mmol) in dry acetone (20 mL) was stirred at reflux overnight. After being cooled to room temperature, the solvent was removed under reduced pressure, and the residue was extracted with ethyl acetate (20 mL×3), washed with water (50 mL) and brine (50 mL). The combined organic layer was dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford crude product, which was purified by column chromatography to afford 1,2,3,4-tetrahydro-5-methoxynaphthalene (IIb; 5.47 g, yield: 100%). MS (ESI) m/z (M+H)+ 1.63.
	With potassium hydroxide

With potassium carbonate In acetone at 50℃; for 18h;

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - US2005/153366, 2005, A1 Location in patent: Page/Page column 19-20
[2]Current Patent Assignee: BEIJING KAWIN TECHNOLOGY - US2011/152246, 2011, A1 Location in patent: Page/Page column 114-115
[3]Sergiewskaja; Lipowitsch [Zhurnal Obshchei Khimii, 1950, vol. 20, p. 1171,1172; engl. Ausg. S. 1215, 1216]
[4]Liu, Luo-Yan; Qiao, Jennifer X.; Yeung, Kap-Sun; Ewing, William R.; Yu, Jin-Quan [Journal of the American Chemical Society, 2019, vol. 141, # 37, p. 14870 - 14877]

7
[ 529-35-1 ]
[ 20098-48-0 ]
[ 61038-01-5 ]

Reference： [1]Patent: DE2509037,1976,
Chem.Abstr.,1976,vol. 85

8
[ 41459-42-1 ]
[ 529-35-1 ]
[ 93889-75-9 ]

Reference： [1]Journal of Medicinal Chemistry,1991,vol. 34,p. 1675 - 1692

9
[ 358-23-6 ]
[ 529-35-1 ]
[ 101533-70-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With pyridine for 1h; Cooling with ice;	6.3 Synthesis of Compound 5c (Trifluoro-methanesulfonic Acid 5,6,7,8-tetrahydro-naphthalen-1-yl ester) 5,6,7,8-Tetrahydro-naphthalen-1-ol (10 g, 67.6 mmol) was added to dry pyridine (55 mL), and the mixture cooled with iced water with stirring. Triflic anhydride (13.6 mL, 81.1 mmol) was added thereto and the mixture was stirred. After 1 hour, water was added thereto, and the mixture was extracted from ethyl acetate. Water was removed from the solution in anhydrous MgSO4. The solvent was removed with a rotary evaporator. The residue was separated by column chromatography to obtain a white oily compound 5c (18 g, 99%).
99%	With pyridine for 1h; Cooling with ice;	6.3 (3) Synthesis of Compound 5c ( Trifluoro-methanesulfonic acid 5,6,7,8-tetrahydro-naphthalen-1-yl ester) 5,6,7,8-Tetrahydro-naphthalen-1-ol (10 g, 67.6 mmol) was added to dry pyridine (55 mL), and the mixture cooled with iced water with stirring. Triflic anhydride (13.6 mL, 81.1 mmol) was added thereto and the mixture was stirred. After 1 hour, water was added thereto, and the mixture was extracted from ethyl acetate. Water was removed from the solution in anhydrous MgSO4. The solvent was removed with a rotary evaporator. The residue was separated by column chromatography to obtain a white oily compound 5c (18 g, 99%).
99%	With pyridine for 1h; Cooling with ice;	6.3 Synthesis of Compound 5c 5,6,7,8-tetrahydronaphthalene-1-ol 10g (67.6mmol) was cooled in ice water while stirring and placed in dry pyridine (55mL). Triflic anhydride,13.6mL (81.1mmol) were added into the mixture. After one hour, put water and extracted with ethyl acetate, water was removed with anhydrous MgSO 4 the solution, after removal of the solvent on a rotary evaporator, the compounds of the white oil was separated by column chromatography 5c (18g, 99% ) was obtained.

95.18%	With triethylamine In 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran at 20℃; for 1.5h; Cooling with ice;	477.1 Step 1: tetralin-5-yl trifluoromethanesulfonate Tetralin-5-ol (500 mg, 3.37 mmol) and N,N-diethylethanamine (512.09 mg, 5.06 mmol, 705.36 uL) were dissolved in DCM (5 mL). trifluoromethylsulfonyl trifluoromethanesulfonate (1.14 g, 4.05 mmol, 679.91 uL) was added atice-bath, and the mixture was stirred at RT for 1.5 h. The mixture was poured into water (50 mL) and extracted three times with DCM (50 mL). The combined organic layers were dried (MgSO4), and concentrated. The residue obtained was purified by column chromatography of silica gel eluting with PE/EA (10/1) to give tetralin-5-yl trifluoromethanesulfonate (900 mg, 3.21 mmol, 95.18% yield) as light-yellow oil.
91%	With triethylamine In dichloromethane at 0℃; for 3.25h;
85%	In dichloromethane at 0 - 25℃; for 4h;	11.11A Example 11A: To a solution of tetralin-5-ol (5 g, 33.74 mmol, 1 eq) and Et3N (10.24 g, 101 mmol, 14 mL, 3 eq) in DCM (50 mL) at 0 °C was added dropwise trifluorom ethyl sulfonyl trifluoromethanesulfonate (10.47 g, 37.11 mmol, 6.12 mL, 1.10 eq). The reaction mixture was warmed to 25 °C and stirred for 4 hours. To the mixture was added water (50 mL) and the mixture extracted with DCM (25 mL * 3). The combined organics were dried over anhydrous sodium sulfate and concentrated in vacuo to afford the crude product. The crude product was purified by flash chromatography on silica gel (eluent: petroleum ether) to give the product as an oil (8 g, 85% yield). 1H MR (400 MHz, CD3OD) δ 7.26 - 7.13 (m, 2H), 7.10 (d, J=7.8 Hz, 1H), 2.84 (t, J=5.6 Hz, 2H), 2.78 (t, J=5.6 Hz, 2H), 1.89 - 1.76 (m, 4H).
85%	With triethylamine In dichloromethane at 0 - 25℃; for 4h;	124A To a solution of tetralin-5-ol (5 g, 33.74 mmol, 1 eq) and Et3N (10.24 g, 101 mmol, 14 mL, 3 eq) in DCM (50 mL) at 0 °C was added dropwise trifluorom ethyl sulfonyl trifluoromethanesulfonate (10.47 g, 37.11 mmol, 6.12 mL, 1.1 eq). The reaction mixture was warmed to 25 °C and stirred for 4 hours. To the mixture was added water (50 mL) and the mixture extracted with DCM (25 mL * 3). The combined organics were dried over anhydrous sodium sulfate and concentrated in vacuo to afford the crude product. The crude product was purified by flash chromatography on silica gel (eluent: petroleum ether) to give the product as an oil (8 g, 85% yield). [0232] MR (400 MHz, CD3OD) δ 7.26 - 7.13 (m, 2H), 7.10 (d, J=7.8 Hz, 1H), 2.84 (t, J=5.6 Hz, 2H), 2.78 (t, J=5.6 Hz, 2H), 1.89 - 1.76 (m, 4H).
68%	With triethylamine In dichloromethane for 67.5h;
61%	With dmap In dichloromethane at 20℃; for 10h; Inert atmosphere;	6.6.5.a To a stirred solution of 5,6,7,8-tetrahydronaphthalen-i-ol (5 g, 0.03 mol) in dichloromethane (50 mL) DMAP (7.0 g, 0.057 mol) was added under nitrogen atmosphere. Trifilic anhydride (14.25 g, 0.05 mol) was added drop wise in 10 minutes. It was allowed to stir at ambient temperature for 10 hours. TLC showed complete conversion was taken place. Water (100 mL) was added to the reaction mixture and extracted with dichloromethane (2 x 50 mL). The combined organic layer was dried over magnesium sulfate and concentrated to afford crude compound, which was purified through column chromatography (silica: 100-200 mesh; eluent: 5% ethyl acetate in hexane) to afford the desired compound (9.0 g, 61% yield).
46%	With triethylamine In dichloromethane at -10 - 0℃; Inert atmosphere;	Preparation of trifluoro-methanesulfonic acid5, 6, 7, 8-tetrahydro-naphthalen-1-yl ester (13). Preparation of trifluoro-methanesulfonic acid5, 6, 7, 8-tetrahydro-naphthalen-1-yl ester (13). To a mixture of 5, 6, 7, 8-tetrahydronaphthalene-1-ol 12(1.44g, 9.72mmol, 1eq) and TEA (1.18g, 11.66mmol, 1.2eq) in anhydrous DCM was colded to -10oC and added a solution of traflate anhydride (3.29g, 11.66mmol, 1.2eq) in anhydrous DCM dropwise. After addition, the reaction was stirred at 0oC for 2h, and then quenched by saturated sodium bicarbonate solution at 0oC. DCM was added and the organic layer was separated. Washed by brine and dried over Na2SO4, the organic layer was evaporated to dryness to give brownish oil, which was purified by flash chromatography on silica gel to get colorless oil 1.83g, yield 67%.

Reference： [1]Current Patent Assignee: LG CHEM CO.,LTD. - US2014/77166, 2014, A1 Location in patent: Paragraph 0118
[2]Current Patent Assignee: LG CHEM CO.,LTD. - US2014/77165, 2014, A1 Location in patent: Paragraph 0118-0120
[3]Current Patent Assignee: LG CHEM CO.,LTD. - JP5847151, 2016, B2 Location in patent: Paragraph 0082
[4]Current Patent Assignee: SHANGPHARMA INNOVATION INC; SCRIPPS RESEARCH - WO2021/263278, 2021, A1 Location in patent: Paragraph 002380-002382
[5]Dogga, Bhushanarao; Joseph, Jayan T.; Kumar, C. S. Ananda [European Journal of Organic Chemistry, 2021, vol. 2021, # 2, p. 309 - 313]
[6]Current Patent Assignee: CHRYSALIS INVESTMENTS LIMITED - WO2017/143011, 2017, A1 Location in patent: Paragraph 0158; 0159
[7]Current Patent Assignee: CHRYSALIS INVESTMENTS LIMITED - WO2017/214413, 2017, A1 Location in patent: Paragraph 0231-0232
[8]Fuse, Hiromu; Kojima, Masahiro; Mitsunuma, Harunobu; Kanai, Motomu [Organic Letters, 2018, vol. 20, # 7, p. 2042 - 2045]
[9]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2010/127855, 2010, A1 Location in patent: Page/Page column 104
[10]Lei, Fan; Qu, Boyi; Li, Xiaolong; Guo, Li; Guan, Mei; Hai, Li; Jin, Hui; Wu, Yong [Synthetic Communications, 2014, vol. 44, # 19, p. 2879 - 2885]
[11]Hanack, Michael; Rieth, Robert [Chemische Berichte, 1987, vol. 120, p. 1659 - 1666]

10
[ 91586-32-2 ]
[ 529-35-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	In quinoline at 260℃; for 4h;

Reference： [1]Boger, Dale B.; Mullican, Michael D. [Journal of Organic Chemistry, 1984, vol. 49, # 21, p. 4033 - 4044]

11
[ 529-35-1 ]
[ 100-39-0 ]
[ 89682-88-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate In butanone Heating;
	With potassium carbonate In acetone	3 1-Benzyloxy-5,6,7,8-tetrahydronaphthalene (3) EXAMPLE 3 1-Benzyloxy-5,6,7,8-tetrahydronaphthalene (3) 5,6,7,8-tetrahydro-1-naphthol (5.9 g, 39mM) was added to a suspension of potassium carbonate (8.3 g, 60mM) in acetone (100 ml) and heated under reflux for 0.5 hour. Benzyl bromide (7.5 g, 43.8mM) was then added and the mixture was heated under reflux for a further 3 days with stirring. The resulting suspension was filtered and the filtrate was evaporated under reduced pressure to give an oil. This oil was dissolved in ether, washed with water, dried (sodium sulphate) and evaporated to giving an oil which was distilled under high vacuum to give the benzyl ether (3) (9.4 g, b.p. 170°-176° C. at 0.8 mm Hg).
	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 21h;	29 Reference Example 29 Reference Example 29 A mixture of 5,6,7,8-tetrahydro-1-naphthol (4.96 g), benzylbromide (4.3 mL), potassium carbonate (6.94 g), and N,N-dimethylformamide (70 mL) was stirred at room temperature for 21 hours. The reactant was poured into water and extracted with ethyl acetate. The extracts were washed with water, dried and concentrated. The obtained residue was purified by silica gel column chromatography to obtain 5-(benzyloxy)-1,2,3,4-tetrahydronaphthalene (7.85 g). 1H-NMR (300 MHz, CDCl3) δ: 1.72-1.84 (4H, m), 2.72-2.78 (4H, m), 5.05 (2H, s), 6.68-6.72 (2H, m), 7.04 (1H, d, J=7.8 Hz), 7.27-7.45 (5H, m).

Reference： [1]Gu; Weiss [Journal of Organic Chemistry, 2001, vol. 66, # 5, p. 1775 - 1780]
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4539319, 1985, A
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1553074, 2005, A1 Location in patent: Page/Page column 42

12
[ 529-35-1 ]
[ 54899-73-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With NBS In acetonitrile at 0 - 25℃; for 4h;
86%	With hydrogen bromide; dimethyl sulfoxide In lithium hydroxide monohydrate; ethyl acetate at 60℃; for 0.25h;
70%	With NBS In acetonitrile at 20℃; for 48h;

	With tributylammonium tribromide
	With tetra-N-butylammonium tribromide In dichloromethane	2-2 General Procedure 2-2: Synthesis of 4-(benzyloxy)-5,6,7,8-tetrahydronaphthalen-l- ylboronic acid[00186] Synthesis of the title compound was conducted according to procedures described by John A. Lowe, III, inJ. Med. Chem., 2004, 47, 1575-1586. Specifically, 4-bromo-l-naphthol was prepared from 1-napthol by treating with 1 equivalent of tributylammonium tribromide. It was then dissolved in acetonitrile, treated with benzyl bromide and potassium carbonate, and heated under reflux for 14 hours to provide 4-bromo-l-benzyloxynaphthalene. The compound 4-bromo-l-benzyloxynaphthalene then reacted with n-butyllithium and tri ethyl borate to afford the title compound.
13 grams (22.9 %)	With bromine In Carbon tetrachloride	III Preparation of 4-Bromo-5,6,7,8-tetrahydro-1-naphthol EXAMPLE III Preparation of 4-Bromo-5,6,7,8-tetrahydro-1-naphthol To a solution of 37 grams (0.25 mole) of 5,6,7,8-tetrahydronaphthol in 150 ml of carbon tetrachloride was added dropwise with stirring a solution of 44 grams (0.25 mole) of bromine in 50 ml of carbon tetrachloride. When the addition was complete the mixture was stirred for 30 minutes at room temperature and then evaporated in vacuo to a residue which after two recrystallizations from hexane provided 13 grams (22.9 percent) of product, m.p. 83°-85°C. Anal. Calc'd. for C10 H11 BrO: C, 52.86; H, 4.88. Found: C, 52.99; H, 4.73.
	With NBS In acetonitrile at 25℃; for 16h; Inert atmosphere;	1.1 Step 1: Synthesis of compound WX001-2 Add WX001-1 (5 g, 33.74 mmol) and acetonitrile (50 mL) to the pre-dried reaction flask, add N-bromo-succinimide (6.61 g, 37.11 mmol), replace nitrogen three times, and place at 25°C Stir for 16 hours. After the reaction was completed, the reaction solution was directly concentrated under reduced pressure, and the concentrate was added with methyl tert-butyl ether (200 mL) to make a slurry, slurried at 25° C. for 30 minutes, filtered, and the filtrate was collected. The filtrate was washed with saturated brine (200 mL*2), The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain WX001-2.

Reference： [1]Uyanik, Muhammet; Yasui, Takeshi; Ishihara, Kazuaki [Angewandte Chemie - International Edition, 2013, vol. 52, # 35, p. 9215 - 9218][Angew. Chem., 2013, vol. 125, # 35, p. 9385 - 9388]
[2]Song, Song; Sun, Xiang; Li, Xinwei; Yuan, Yizhi; Jiao, Ning [Organic Letters, 2015, vol. 17, # 12, p. 2886 - 2889]
[3]Phipps, Robert J.; Toste, F. Dean [Journal of the American Chemical Society, 2013, vol. 135, # 4, p. 1268 - 1271]
[4]Lowe III, John A.; Qian, Weimin; Drozda, Susan E.; Volkmann, Robert A.; Nason, Deane; Nelson, Robert B.; Nolan, Charles; Liston, Dane; Ward, Karen; Faraci, Steve; Verdries, Kim; Seymour, Pat; Majchrzak, Michael; Villalobos, Anabella; White, W. Frost [Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1575 - 1586]
[5]Current Patent Assignee: BIOGEN IDEC INC. - WO2008/94575, 2008, A2 Location in patent: Page/Page column 52
[6]Current Patent Assignee: SANOFI - US3958006, 1976, A
[7]Current Patent Assignee: WUXI APPTEC CO., LTD. - WO2022/53028, 2022, A1 Location in patent: Page/Page column 15-16

13
[ 21336-06-1 ]
[ 529-35-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With [(tris(1-pyrazolyl)borate)Ru(P(phenyl)3)(CH₃CN)2]PF₆; water In various solvent(s) at 100℃; for 24h;

Reference： [1]Odedra, Arjan; Wu, Chang-Jung; Pratap, Taduri Bhanu; Huang, Chun-Wei; Ran, Ying-Fen; Liu, Rai-Shung [Journal of the American Chemical Society, 2005, vol. 127, # 10, p. 3406 - 3412]

14
[ 529-35-1 ]
[ 115314-14-2 ]
C₁₃H₁₆O₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 3067 - 3076

15
[ 529-35-1 ]
[ 106-89-8 ]
[ 4051-92-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With cesium fluoride In N,N-dimethyl-formamide at 50℃; for 16h;
	With sodium methylate In methanol	8 Synthesis of compound (6) R= STR14 EXAMPLE 8 Synthesis of compound (6) R= STR14 5,6,7,8-Tetrahydro-1-naphthol is allowed to react with sodium methoxide in methanol to give the corresponding sodium salt which is further allowed to react with epichlorohydrin to give 1-(2,3-epoxypropoxy)-5,6,7,8-tetrahydronaphthalene (cf.

Reference： [1]Fagerstroem, Alexandra; Nilsson, Mikael; Berg, Ulf; Isaksson, Roland [Organic and Biomolecular Chemistry, 2006, vol. 4, # 16, p. 3067 - 3076]
[2]Current Patent Assignee: NIPPON SHINYAKU CO LTD - US4435397, 1984, A

16
[ 529-35-1 ]
[ 7474-90-0 ]

Yield	Reaction Conditions	Operation in experiment
60%	With methylene blue In methanol; water at 20℃; for 0.666667h; Irradiation; Flow reactor;
	Multi-step reaction with 2 steps 1: 1) diazonium salt of sulfanilic acid, 2.) Na₂S₂O₄ 2: K₂Cr₂O₇, 5percent aq. H₂SO₄ / CH₂Cl₂
	Multi-step reaction with 3 steps 1: 1) Sodium nitrite , aq. HCl 2) aq. NaOH / 2) stand overnight 2: Sodium hydrosulfite / H₂O / 5 h / Ambient temperature 3: 6.8 g / aq. H₂SO₄, MnO₂ / Heating

Reference： [1]Wellauer, Joël; Miladinov, Dragan; Buchholz, Thomas; Schütz, Jan; Stemmler, René T.; Medlock, Jonathan A.; Bonrath, Werner; Sparr, Christof [Chemistry - A European Journal, 2021, vol. 27, # 38, p. 9748 - 9752]
[2]Kallmayer; Seyfang [Archiv der Pharmazie, 1985, vol. 318, # 7, p. 607 - 614]
[3]Malesani, Giorgio; Ferlin, Maria Grazia; Masiero, Sergio [Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 633 - 637]

17
[ 529-35-1 ]
[ 540-72-7 ]
[ 600176-44-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: 5,6,7,8-Tetrahydronaphthalen-1-ol; sodium thiocyanide With sodium bromide In acetonitrile at 20℃; for 0.0833333h; Stage #2: With bromine In acetonitrile for 2h;	YY Thiol YY ; Preparation of 4-Thiocyanato-5,6,7,8-tetrahydro-naphthalen-1-ol (Compound YYA) Thiol YY Preparation of 4-Thiocyanato-5,6,7,8-tetrahydro-naphthalen-1-ol (Compound YYA) 5,6,7,8-Tetrahydro-naphthalen-1-ol (1 g, 6.8 mmol) was dissolved in 25 ml acetonitrile.Sodium thiocyanate (1.76 g, 22 mmol) and sodium bromide (0.7 g, 6.8 mmol) were added and stirred for 5 minutes at ambient temperature.bromine (1.2 g, 7.48 mmol) was added drop wise over 5 minutes.The orange solution was allowed to stir two hours.brine was added and the crude product was extracted twice into ethyl acetate.The combined organic extracts were washed once with brine, dried over anhydrous sodium sulfate, decanted and concentrated.Normal phase chromatography afforded the title product, 1.28 g, 92%. 400 MHz 1H NMR (DMSO-d6) δ 11.1 (s, 1H), 7.40 (d, 1H, J=8.8 Hz), 6.61 (d, 1H, 8.8 Hz), 2.78 (m, 2H), 2.59 (m, 2H), 1.70 (m, 4H). MS m/z 278 (m+1)

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/225158, 2003, A1 Location in patent: Page 84

18
[ 529-35-1 ]
[ 329972-27-2 ]
2-Furan-2-yl-7-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In 1-methyl-pyrrolidin-2-one at 160℃; for 2h;	258 EXAMPLE 258 2-Furan-2-yl-7-(5,6,7,8-tetrahydronaphthalen-1-yloxy)[1,2,4]triazolo[1,5-a]pyridin-5-ylamine EXAMPLE 258 2-Furan-2-yl-7-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine A mixture of 1 eq. 7-bromo-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine, 5 eq. 5,6,7,8-tetrahydro-naphthalen-1-ol and a catalytic amount of CS2CO3 in 200 μl N-methyl-pyrrolidon was heated for 2 h to 160°. The mixture was, after filtration, purified with reversed phase column chromatography eluting with an acetonitrile/water gradient yielding the title compound, MS m/e (%): 346 M+H+ (100%).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US6355653, 2002, B1 Location in patent: Page column 125-126

19
[ 32161-06-1 ]
[ 529-35-1 ]
[ 443131-03-1 ]

Yield	Reaction Conditions	Operation in experiment
66%	With boron trifluoride diethyl etherate; In tetrahydrofuran; at 20 - 100℃; for 16h;	[1- 4- (1-HVDROXV-5, 6, 7. 8-TETRAHVDRO-NAPHTHALEN-2-YL)-3, 6-DIHYDRO-2H-] [PYRIDIN-1-VLL-ETHANONE] To a solution of 5,6, 7, 8-tetrahydro-naphthalen-1-ol (20.0 g, 0.135 mol) and [1-ACETYL-] [4-PIPERIDONE (22.84 G, 1 : 2 EQ. ) IN THF (400 ML), WAS ADDED DROPWISE BF3-ET2O (68] mL, 4.0 eq). The mixture was stirred at [100XB0;C] for 2 hours, and 14 hours at room temperature. The mixture was treated with a 1 N HCI solution (400 mL). The resulting solution was extracted with DCM. The organic layer was dried over [NA2SO4 AND] evaporated to dryness to give an oil which was recrystallized in acetonitrile to give the title compound (24.2 g, 89 [MMOL)] as white crystals in 66% yield
66%	With boron trifluoride diethyl etherate; In tetrahydrofuran; at 20 - 100℃; for 16h;	To a solution of the available 5,6, 7, 8-tetrahydro-naphthalen-1-ol (20.0 g, 0.135 mol) [AND 1-ACETYL-4-PIPERIDONE (22.84 G, 1.2 EQ. ) IN THF (400 ML) WAS ADDED DROPWISE] [BFS-ETZO] (68 mL, 4.0 [EQ).] The mixture was stirred at [100XB0;C] for 2 hours, and 14 hours at room temperature. The mixture was treated with a 1 N HCI solution (400 mL). The resulting solution was extracted with DCM. The organic layer was dried over [NA2SO4] and evaporated to dryness to give an oil which was recrystallized from acetonitrile to give the title compound (24.2 g, 89 [MMOL)] as white crystals in a [66% YIELD ; GC/MS] : [M+ C, 7H20NO2 271.]
66%	boron trifluoride diethyl etherate; In tetrahydrofuran; at 20 - 100℃; for 16h;	to a solution of 5,6,7,8-tetrahydro-naphthalen-l-ol (20.0 g, 0.135 mol) and 1-acetyl- 4-piperidone (22.84 g, 1.2 eq. ) in THF (400 ml), was added dropwise BF3-Et2O (68 ml, 4.0 eq). The mixture was stirred at 100C for 2 hours, and 14 hours at room temperature. The mixture was treated with a 1 N HCI solution (400 ml). The resulting solution was extracted with DCM. The organic layer was dried over Na2S04 and evaporated to dryness to give an oil which was recrystallized in acetonitrile to give the title compound (24.2 g, 89 mmol) as a white crystals in a 66% yield ; GC/MS: M+ C17H2ONO2 271.

66%

With boron trifluoride diethyl etherate; In tetrahydrofuran; at 20 - 100℃; for 16h;

To a solution of the available 5,6, [7, 8-TETRAHYDRO-NAPHTHALEN-1-OL (20.] 0 g, 0.135 mol) [ AND 1-ACETYL-4-PIPERIDONE (22.84 G, 1.2 EQ. ) IN THF (400 ML), WAS ADDED DROPWISE] [BF3-ET2O] (68 mL, 4.0 eq). The mixture was stirred at [100C] for 2 hours and 14 hours at room temperature. The mixture was treated with a [1 N HCI SOLUTION] (400 mL). The resulting solution was extracted with DCM. The organic layer was dried over [NA2SO4] and evaporated to dryness to give an oil which was recrystallized in acetonitrile to give the title compound (24.2 g, 89 [MMOL)] as a white crystals in a 66% yield ; GC/MS: [M. C17H20NO2 271.]

Reference： [1]Patent: WO2004/6922,2004,A1 .Location in patent: Page/Page column 30
[2]Patent: WO2004/6923,2004,A1 .Location in patent: Page/Page column 22
[3]Patent: WO2004/6924,2004,A1 .Location in patent: Page/Page column 21
[4]Patent: WO2004/7493,2004,A1 .Location in patent: Page 21-22

20
[ 90-15-3 ]
[ 529-35-1 ]
[ 529-33-9 ]
[ 529-34-0 ]

Yield	Reaction Conditions	Operation in experiment
	With carbon dioxide; hydrogen at 50℃; for 0.75h;	13 0.2014 g of 1-naphthol and 0.0205 g of an activated charcoal-supported rhodium catalyst (amount of metal supported 5%, made by Wako Chemicals) were put into a stainless steel high-pressure reactor of internal volume 50 ml, a pressure of 3.0 MPa of hydrogen and a pressure of 16 MPa of carbon dioxide were introduced in, and hydrogenation was carried out for 45 minutes at a reaction temperature of 50°C. After reaction had been completed, the hydrogen and carbon dioxide were released, and the products obtained were recovered by acetone extraction, and then analyzed using a gas chromatograph-mass spectrometer. The 1-naphthol conversion ratio was 79.5%, and the selectivities were 72.8% for 5,6,7,8-tetrahydronaphthol, 11.5% for 1,2,3, 4-tetrahydronaphthol and 4.6% for tetralone, the selectivity for hydrogenation being 98.6%. Moreover, the selectivities were 0.9% for tetralin and 0.5% for decalin, which are byproducts, and hence it is thought that the selectivity for dehydration of the 1-naphthol was 1.4%.

Reference： [1]Current Patent Assignee: NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY - EP1637512, 2006, A1 Location in patent: Page/Page column 12

21
[ 769-54-0 ]
[ 529-35-1 ]
[ 497-19-8 ]
[ 130865-37-1 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	EXAMPLE 5 4-Nitro-3-(5,6,7,8-tetrahydro-1-naphthyloxy)pyridine-N-oxide To 5,6,7,8-tetrahydro-1-naphthol (6.0 g) in DMF (100 ml) was added Na2 CO3 (10 g) portionwise at room temperature. Then a solution of <strong>[769-54-0]3-fluoro-4-nitropyridine-N-oxide</strong> (6.0 g) in 20 ml of DMF was added dropwise and the mixture was stirred at room temperature for four hours. The mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried (sat NaCl, anhy. MgSO4). After filtration, the solvent was evaporated to yield a solid (12.2 g), which was eluted with 2.5% ethyl acetate/DCM on a silica gel column via HPLC. The desired fractions were concentrated to yield a solid (9.8 g). Of this material, 4.8 g was recrystallized from absolute ethanol to yield a solid, 2.8 g, m.p. 109-111 C. Analysis: Calculated for C15 H14 N2 O4: 62.93% C, 4.93% H, 9.79% N; Found: 62.93% C, 4.88% H, 9.74% N.

Reference： [1]Patent: US4931457,1990,A

22
[ 529-35-1 ]
[ 106-96-7 ]
[ 20009-51-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In toluene; acetonitrile at 20℃;	6.A 5-(Prop-2-ynyloxy)-1,2,3,4-tetrahydronaphthalene 5,6,7,8-Tetrahydronaphthalen-1-ol (Aldrich, 3.93 g, 26.5 mmol), propargyl bromide (80% in toluene, 3.9 ml, 35 mmol), and potassium carbonate (4.83 g, 35 mmol) were stirred together in acetonitrile (75 mL) for 6 days at ambient temperature. The solvent was removed under reduced pressure, and the residue taken into water and extracted with diethyl ether. The organic layers were combined, dried with magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.76 (m, 4H), 2.49 (t, J=2.37 Hz, 1H), 2.68 (t, J=5.59 Hz, 2H), 2.75 (t, J=5.59, 2H), 4.69 (d, J=2.37 Hz, 2H), 6.74 (dd, J=7.80, 3.73 Hz, 2H), 7.06 (t, J=7.80 Hz, 1H). MS (DCI) m/z 187.06 (M+H)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2008/153871, 2008, A1 Location in patent: Page/Page column 17-18

23
[ 4341-76-8 ]
[ 529-35-1 ]
[ 1191998-20-5 ]

Yield	Reaction Conditions	Operation in experiment
72%	With dmap; potassium carbonate In tetrahydrofuran at 25 - 85℃;	98 acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide A mixture of 5,6,7,8-tetrahydro-naphthalen-1-ol (3.00 g, 20.24 mmol) and ethyl-2-butynoate (13.62 g, 121.46 mmol) in tetrahydrofuran (100 mL) was treated with potassium carbonate (3.10 g, 22.43 mmol) and 4-dimethylaminopyridine (0.26 g, 2.12 mmol). The reaction was then heated at 85° C. overnight. At this time, the reaction was cooled to 25° C. and was stirred at 25° C. overnight. At this time, the reaction was concentrated in vacuo. The residue was dissolved in ethyl acetate (200 mL) and was washed with water (1100 mL) and a saturated aqueous sodium chloride solution (1100 mL). The organics were then dried over magnesium sulfate, filtered, rinsed with ethyl acetate and concentrated in vacuo. The material was taken up in ethyl acetate and absorbed onto silica gel. Purification by Analogix flash chromatography (115 g, 1-10% ethyl acetate/hexanes) afforded 3-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-but-2-enoic acid ethyl ester (3.82 g, 72%) as a light yellow oil: HR-ES-MS m/z calculated for C26H34N4O5 [M+H]+ 483.2602, observed 483.2603; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.11 (t, J=7.1 Hz, 3H), 1.61-1.77 (m, 4H), 2.44 (s, 3H), 2.46 (br. s., 2H), 2.76 (br. s., 2H), 3.98 (q, J=7.1 Hz, 2H), 4.57 (s, 1H), 6.84 (d, J=7.7 Hz, 1H), 7.03 (d, J=7.7 Hz, 1H), 7.18 (t, J=7.7 Hz, 1H).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2009/264445, 2009, A1 Location in patent: Page/Page column 80

24
[ 529-35-1 ]
[ 2284-20-0 ]
[ 1207740-48-4 ]

Yield	Reaction Conditions	Operation in experiment
41%	Stage #1: 5,6,7,8-Tetrahydronaphthalen-1-ol; 4-Methoxyphenyl isothiocyanate With aluminum (III) chloride In dichloromethane at 0 - 20℃; Stage #2: With water In dichloromethane	4.1 Example 4: Synthesis of Compound 8; STEP-I: To a solution of 320 mg (2.16 mmol) of phenol 7 and 357 mg (2.16 mmol) of 4- methoxyphenyl isothiocyanate in 25 mL of methylene chloride was slowly added 431 mg (3.24 mmol) of aluminum trichloride in one portion at 00C. The resulting solution was stirred at 00C for 30 min, allowed to warm to room temperature and continued to stir for 2 h. The reaction mixture was quenched by dropwise addition of 20 mL of water and stirring for 5 min. The layers were separated and the aqueous phase was extracted twice with 20-mL portions of methylene chloride. The combined organic fractions were dried (Na2SO4) and concentrated in vacuo. The residue solid was chromatographed over silica gel (eluted with 9:1 hexanes-ethyl acetate → 1 :1 hexanes-ethyl acetate → ethyl acetate) to afford 275 mg (41%) of thioamide 8 as a light yellow solid. 1H NMR (400 MHz, DMSO) δ 11.59 (s, IH), 11.27 (s, IH), 7.52 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.0 Hz, IH), 7.00 (d, J= 8.8 Hz, 2H), 6.68 (d, J= 8.0 Hz, IH), 3.79 (s, 3H), 2.76 - 2.65 (m, 2H), 2.65 - 2.54 (m, 2H), 1.80 - 1.63 (m, 4H).

Reference： [1]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2010/17479, 2010, A1 Location in patent: Page/Page column 112-113

25
[ 914774-92-8 ]
[ 529-35-1 ]
1-hydroxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid (2-chloro-4-trifluoromethanesulfonyl-phenyl)-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5,6,7,8-Tetrahydronaphthalen-1-ol With boron trichloride In dichloromethane at -10℃; for 0.0833333h; Stage #2: 2-chloro-1-isocyanato-4-trifluoromethanesulfonyl-benzene In dichloromethane at 40℃; Heating / reflux; Stage #3: With hydrogenchloride In diethyl ether; dichloromethane; water at 20℃; for 4h;	B; 20 Boron trichloride catalyzed ortho carbamoylation of phenols may be achieved by a method similar to that described by O. Piccolo, L. Filippini, L. Tinucci, Tetrahedron, 1986, 42 (3), 885-892, as follows: A solution of the phenol I (1 mmol) in dichloromethane (5 ml) is added to a stirred solution of boron trichloride (1M in dichloromethane, 1-1.1 mmol) under nitrogen at -10 °C. After 5 minutes, a solution of the aryl isocyanate II (1-1.1 mmol) in dichloromethane (5 ml) is added. The resulting mixture is stirred under reflux for 2 h, then at ~ 40 °C overnight. The mixture is cooled to room temperature and stirred for 4 h after the addition of 4 M HCI (10 ml), and diethyl ether (25 ml) is then added. If a precipitate forms it is filtered off, rinsed with a small amount of diethyl ether and dried to give the anilide III. If no well-defined precipitate forms, the organic layer is separated, dried, and the solvent is evaporated. The crude product may be purified by column chromatography.

Reference： [1]Current Patent Assignee: GAODIAN PHARMACEUTICAL - WO2006/120178, 2006, A1 Location in patent: Page/Page column 42; 57

26
[ 5445-17-0 ]
[ 529-35-1 ]
[ 73943-50-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In N,N-dimethyl-formamide at 170℃; for 0.166667h; Microwave irradiation;	Methyl 2-[(2,3-dimethylphenyl)oxy]propanoate (6) General Procedure: In a 20mL Biotage microwave vial was added 2,3-dimethylphenol (400 mg, 3.27 mmol) dissolved in 15 mL dimethyl formamide (DMF), potassium carbonate (677 mg, 4.91mmol) and methyl 2-bromopropanoate (0.552 mg, 3.27 mmol). The reaction vessel was then sealed and irradiated for 10 min at 170 °C. After the reaction was complete, the reaction mixture was diluted with water and the desired compound was extracted out of solution with diethyl ether. The ether layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting compound was used immediately in the next reaction without further purification.

Reference： [1]Evans, Karen A.; Shearer, Barry G.; Wisnoski, David D.; Shi, Dongchuan; Sparks, Steven M.; Sternbach, Daniel D.; Winegar, Deborah A.; Billin, Andrew N.; Britt, Christy; Way, James M.; Epperly, Andrea H.; Leesnitzer, Lisa M.; Merrihew, Raymond V.; Xu, Robert X.; Lambert, Millard H.; Jin, Jian [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 8, p. 2345 - 2350]

27
[ 529-35-1 ]
[ 623-47-2 ]
[ 105901-61-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With palladium diacetate; trifluoroacetic acid at 0 - 20℃;	(a) Synthesis of 7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (7a). To an ice-cold solution of compound 6 (0.296 g, 2 mmol) in TFA (2 ml) were added Pd(OAc)2 (6 mg, 0.025 mmol) and ethyl propynoate (0.39 g, 0.41 ml, 4 mmol). The mixture was stirred for 5 min under cooling, stirred for 22 h at room temperature and neutralized with 10% NaHCO3 solution. Extraction with CH2Cl2 (2 × 50 ml), drying of the organic layer (MgSO4), evaporation of the solvent and separation by column chromatography [silica gel, hexane/EtOAc (5:1)] gave, after elution of unreacted starting material (5%), compound 7a (80% yield), light-green crystals, mp 105-106 °C (CH2Cl2), IR (KBr): 1712, 1604 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.75-1.94 (m, 4H), 2.98 (t, 2H, J = 5.5 Hz), 3.04 (t, 2H, J = 5.5 Hz), 6.35 (d, 1H, J = 9.5 Hz), 7.01 (d, 1H, J = 7.7 Hz), 7.21 (d, 1H, J = 7.7 Hz), 7.66 (d, 1H, J = 9.5 Hz); 13C NMR (75.5 MHz, CDCl3) δ 22.0, 22.4, 22.5, 29.9, 114.9, 124.3, 125.2, 125.5, 142.5, 143.9, 152.2, 155.0, 161.2; MS (ESI): 201 [M+H]+·, 223 [M+Na]+·; Anal. Calcd for C13H12O2: C, 77.98; H, 6.04. Found: C, 77.72; H, 6.23.

Reference： [1]Location in patent: experimental part Symeonidis, Theodoros S.; Kallitsakis, Michael G.; Litinas, Konstantinos E. [Tetrahedron Letters, 2011, vol. 52, # 42, p. 5452 - 5455]

28
[ 529-35-1 ]
[ 1367200-61-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 18h; Darkness;	4.2.17. 2,4-Dibromo-5,6,7,8-tetrahydro-1-naphthol (23) To a solution of 5,6,7,8-tetrahydro-1-naphthol 22 (100 mg, 0.675 mmol) in dimethylformamide (3 mL) was added a solution of N-bromosuccinimide (246 mg, 1.38 mmol) in dimethylformamide (1 mL). The solution was stirred at room temperature, in the dark, for 18 h, diluted with water (20 mL), extracted with ethyl acetate (3×10 mL) and the combined organic extracts were washed with water (4×15 mL) and dried (MgSO4). Removal of the solvent under reduced pressure and crystallization from hexane gave the title compound23 (197 mg, 96%) as colourless needles, mp 54-55 °C; νmax 3398br, 2934, 1425, 1301, 1221, 689 cm-1; δH (400 MHz) 1.73-1.80 (4H, m, H26 and H27), 2.64-2.72 (4H, m, H25 and H28), 5.48 (1H, s, OH), 7.50 (1H, s, H3); δC (100 MHz) 21.9 (CH2), 22.5 (CH2), 24.5 (CH2), 30.3 (CH2), 106.8 (C), 115.9 (C), 127.5 (C), 130.9 (CH), 137.5 (C), 149.1 (C); m/z (EI) 308 (M+, 81Br2, 22%), 306 (M+, 81Br79Br, 46%), 304 (M+, 79Br2, 26%), 146 (70), 84 (54), 57 (92), 55 (100), 51 (61); HRMS (ESI): [M-H]-, found 302.9029. C10H979Br2O requires 302.9026.

Reference： [1]Location in patent: experimental part Donner, Christopher D.; Cuzzupe, Anthony N.; Falzon, Cheryl L.; Gill, Melvyn [Tetrahedron, 2012, vol. 68, # 13, p. 2799 - 2805]

29
[ 529-35-1 ]
[ 42075-32-1 ]
[ 1373521-58-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 96h;	1. Preparation of substrates. General procedure: To a solution of o-cresol (11.0 g), o-phenyphenol (11.0 g), or other phenols (3-8 g) with (R,R)-2,4-pentanediol (1.2 equiv) and triphenylphosphine (1.1 equiv) in THF (140 ml) was added dropwise a THF (160 ml) solution of diisopropyl azodicarboxylate (1.2 equiv) at room temperature. After stirring for 4 days, the solution was concentrated, and then purified by column chromatography on silica gel (elution with 20% ethyl acetate in hexane) to give I.

Reference： [1]Im, Chun Young; Sugimura, Takashi [Tetrahedron, 2012, vol. 68, # 19, p. 3744 - 3749]

30
[ 529-35-1 ]
[ 999-97-3 ]
(5,6,7,8-tetrahydro-naphthalen-1-yloxy)trimethylsilane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With iodine at 20℃; for 2.5h; Neat (no solvent); Air atmosphere;	4.2. Representative procedure of I₂-catalysed reaction of phenols, alcohols and carbohydrates with HMDS under SFRC (small scale) General procedure: Iodine (5.1 mg, 0.02 mmol) was added to phenol 1l (0.148 g, 1 mmol) or alcohol 3h (0.242 g, 1 mmol), followed by addition of HMDS (0.089 g, 0.55 mmol); the mixture was stirred at room temperature until the complete consumption of the starting material (TLC check). The crude reaction mixture was dissolved in 4 mL of hexane/TBME and stirred with the finely powdered Na2S2O3 until the disappearance of iodine. From this point on, two different scenarios are possible: a) The solids were filtered off and the solvent evaporated under the reduced pressure, yielding the crude product. In numerous cases, such products were practically pure; column chromatography and/or distillation improved their quality only slightly. b) A solution of a product in hexane/TBME mixture could be directly subjected to the column chromatography, without filtration of the solids. Caution: Although we experienced no problems when performing these reactions, care should taken due to the potential formation of NI3.

Reference： [1]Location in patent: experimental part Jereb, Marjan [Tetrahedron, 2012, vol. 68, # 20, p. 3861 - 3867]

31
[ 50-00-0 ]
[ 529-35-1 ]
[ 86295-45-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine; magnesium chloride In tetrahydrofuran for 4h; Reflux; Inert atmosphere;	3 Weigh paraformaldehyde (460mg, 15.3mmol) And anhydrous magnesium chloride (324mg, 3.4mmol) in a 50mL two-necked flask, Plug in the condenser tube, Exchange the air in the system with argon, Anaerobic treatment of the device. Then, anhydrous tetrahydrofuran (20 mL) was sequentially added through a syringe. Triethylamine (1.2 mL, 8.5 mmol), A solution of compound 3-1 (300 mg, 2.27 mmol) in anhydrous tetrahydrofuran (5 mL). The system was reacted at reflux for 4h. After the reaction, the system was adjusted to pH = 1 with a 1N hydrochloric acid solution. Extract the aqueous phase with ethyl acetate (20 mL x 3), Combined organic phases, The organic phase was washed with saturated brine (20 mL x 1), Dry over anhydrous sodium sulfate and evaporate the solvent under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate = 400: 1), Compound 3-2 (white solid, 300 mg) was obtained.
81%	With triethylamine; magnesium chloride In tetrahydrofuran Reflux; Inert atmosphere;	Step ii. Synthesis of compound 21 To a dried Schlenk tube were added tetrahydro-1-naphthol (20) (10 g, 67.6 mmol), (CH2O)n (12.2 g, 405 mmol), MgCl2 (9.63 g, 101 mmol), Et3N (37.4 mL), and anhydrous THF (100 mL). The reaction mixture was refluxed overnight under nitrogen, then cooled to room temperature and extracted with ethyl acetate (40 mL × 3). The organic phase was washed with 1 N HCl (50 mL × 2) and dried over anhydrous Na2SO4. The solvent was concentrated via rotary evaporation and the residue was purified by flash column chromatography (silica gel, hexanes / ethyl acetate = 20:1) to afford compound 21 (9.0 g, 81% yield) as a colorless oil.2 21: Colorless oil; IR (KBr) 3037, 2934, 2859, 1651, 1645, 1429, 1309, 1221, 1086, 952, 767 cm-1; 1H NMR (400 MHz, CDCl3) δ 11.15 (s, 1H), 9.50 (s, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 8.0 Hz, 1H), 2.50 (t, J = 5.6 Hz, 2H), 2.41 (t, J = 5.6 Hz, 2H), 1.57-1.46 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 196.0, 160.0, 147.7, 130.0, 125.9, 120.8, 117.8, 30.5, 22.4, 22.2, 22.2.
78%	With triethylamine; magnesium chloride In tetrahydrofuran for 4h; Reflux; Inert atmosphere;

	With triethylamine; magnesium chloride In tetrahydrofuran for 24h; Reflux;
	With triethylamine; magnesium chloride In acetonitrile for 5h; Reflux;

Reference： [1]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY - CN110627817, 2019, A Location in patent: Paragraph 0213-0216
[2]Hou, Chengkang; Zhao, Guoqing; Xu, Dongfang; Zhao, Baoguo [Tetrahedron Letters, 2018, vol. 59, # 11, p. 1028 - 1033]
[3]Čipak Gašparović, Ana; Dömötör, Orsolya; Enyedy, Éva A.; Frank, Éva; Holczbauer, Tamás; Kincses, Annamária; Kiss, Márton A.; May, Nóra V.; Petrasheuskaya, Tatsiana V.; Spengler, Gabriella [New Journal of Chemistry, 2020, vol. 44, # 28, p. 12154 - 12168]
[4]Jin, Zhichao; Yang, Ruojie; Du, Yu; Tiwari, Bhoopendra; Ganguly, Rakesh; Chi, Yonggui Robin [Organic Letters, 2012, vol. 14, # 12, p. 3226 - 3229]
[5]Lee, Jeonghyo; Kang, Bora; Kim, Dongwook; Lee, Jia; Chang, Sukbok [Journal of the American Chemical Society, 2021, vol. 143, # 44, p. 18406 - 18412]

32
[ 529-35-1 ]
[ 106-93-4 ]
[ 928713-60-4 ]

Yield	Reaction Conditions	Operation in experiment
42%	With potassium carbonate; potassium iodide In acetone at 60℃;	General procedure for the synthesis of aryloxylethylbromides derivatives 22{1-11} General procedure: A solution of 1,2-dibromoethane (0.02 mol) in 40 ml of acetone was added dropwise into the mixture of respective phenol 1-11 (0.08 mol) and K2CO3 (0.04 mol) in 30 ml of acetone. Subsequently a catalytic amount of KI (0.3 mmol) was added and the resulting mixture was stirred at 60°C for 24-72 hours. After the completion of the reaction the inorganic residues were filtrated off and organic mixture was concentrated under vacuum. The obtained crude product was purified on silica gel with AcOEt/hexane as eluting system.
37%	With potassium carbonate; potassium iodide In butanone for 48h; Reflux; Inert atmosphere;

Reference： [1]Zajdel, Pawel; Grychowska, Katarzyna; Pawlowski, MacIej; Kurczab, Rafal; Satala, Grzegorz; Bojarski, Andrzej J. [European Journal of Medicinal Chemistry, 2012, vol. 56, p. 348 - 360,13] Zajdel, Paweł; Kurczab, Rafał; Grychowska, Katarzyna; Satała, Grzegorz; Pawłowski, MacIej; Bojarski, Andrzej J. [European Journal of Medicinal Chemistry, 2012, vol. 56, p. 348 - 360]
[2]Valhondo, Margarita; Marco, Isabel; Martín-Fontecha, Mar; Vázquez-Villa, Henar; Ramos, José A.; Berkels, Reinhard; Lauterbach, Thomas; Benhamú, Bellinda; López-Rodríguez, María L. [Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 7851 - 7861]

33
[ 529-35-1 ]
[ 1420230-85-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With (R_a)-4-hydroxy-2,6-bis(2,4,6-tricyclohexylphenyl)dinaphtho-[1,3,2]dioxaphosphepine 4-oxide; sodium carbonate; Selectfluor In toluene at 20℃; for 48h;
75%	With (S)-4-hydroxy-2,6-bis(2,4,6-tricyclohexylphenyl)dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide; sodium carbonate; Selectfluor In toluene at 20℃; for 48h;	14.3 14.1 General procedure for asymmetric fluorination General procedure: To the substrate 1 (0.25 mmol) in a 1 dram (15 x 45 mm) vial equipped with an 8 mm magnetic stirrer bar was added toluene (1.25 ml). Subsequently, anhydrous Na2C03(39.8 mg, 0.375 mmol), Selectfluor (132 mg, 0.375 mmol) and (S)-TCYP (12.4 mg, 0.0125 mmol) were added. The vial was capped with a screw cap and stirred rapidly for the specified time at room temperature, the vial standing on the stirrer plate. After this time, the reaction was diluted with ethyl acetate and poured into satd. NaHC03solution. After extraction, the aqueous layer was extracted with further EtOAc and the combined organics were, dried (Na2S04) and evaporated in vacuo. The crude residue was purified by flash column chromatography. It is notable that fast and efficient stirring should be maintained in order to achieve reliable results.Reaction carried out according to general procedure using 5,6,7,8-Tetrahydro-2- naphthol (37.0 mg, 0.25 mmol) for 40h. Purification by column chromatography, eluting with a gradient of 50 to 80 % CH2CI2in Hexane gave 2a as a colourless oil (17 mg, 0.102 mmol, 41%). Also isolated was a mixture of 2b and 2c as a colourless oil (10 mg, 0.060 mmol, 24%) and 2d as a yellow solid (5 mg, 1 1%).2a: 1H NMR (400 MHz, CDC13) δ 6.82 (dd, J= 10.1 , 6.3 Hz, 1H), 6.21 (dt, J = 10.1 , 1.6 Hz, 1H), 6.06 (s, 1H), 2.63 (tdd, J= 13.3, 5.1 , 1.6 Hz, 1H), 2.43 (d, J= 13.1 Hz, 1H), 2.32 (dddt, J= 14.0, 8.0, 3.9, 2.2 Hz, 1H), 2.05 (dtq, J= 13.8, 4.9, 2.4 Hz, 1H), 1.88 (tt, J= 13.5, 3.9 Hz, 1H), 1.81 - 1.69 (m, 1H), 1.57 - 1.33 (m, 2H).19F NMR (376 MHz, CDC13) δ -155.92 (dt, J= 38.6, 6.7 Hz).13C NMR (151 MHz, CDC13) δ 185.63 (d, J= 4.8 Hz), 158.83 (d, J= 18.7 Hz), 145.94 (d, J= 21.8 Hz), 129.31 (d, J= 7.8 Hz), 123.95 (d, J= 4.7 Hz), 87.43 (d, J= 164.8 Hz), 38.27 (d, J= 25.7 Hz), 32.02 (s), 27.38 (s), 20.50 (d, J= 1.3 Hz), m/z HRMS (EI) found [M]+166.0793, CioHnOiFi requires 166.0794. [a]D20= - 60.6 (c 1.0, CHCI3). HPLC (Chiralpak IC column, 99:01 hexanes/isopropanol, 1 ml/min); tr= 18.1 min (minor), 24.8 min (major); 63% ee.

Reference： [1]Phipps, Robert J.; Toste, F. Dean [Journal of the American Chemical Society, 2013, vol. 135, # 4, p. 1268 - 1271]
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2013/96971, 2013, A1 Location in patent: Paragraph 00123; 00125; 00126; 00129

34
[ 119-64-2 ]
[ 1125-78-6 ]
[ 529-35-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 40% 2: 26%	Stage #1: tetralin With spiro[bicyclo[2.2.1]heptane-2,4′-[1,2]dioxolane]-3′,5′-dione at 40℃; for 48h; Sealed tube; Stage #2: With methylamine In ethanol
	Stage #1: tetralin With phthaloyl peroxide Heating; Stage #2: With water; sodium hydrogencarbonate In methanol at 40℃; Overall yield = 70 %;	General procedure for the hydroxylation of arenes. General procedure: A borosilicate flask was equipped with a magnetic stir bar, and neat or solid arene (0.2-0.8mmol) was added. Addition of hexafluoroisopropanol or trifluoroethanol (2-5 ml) to providea 0.2M solution was followed by the addition of solid phthaloyl peroxide (1, 1.3 equiv.) in portions over 90 s. The reaction flask was placed in a heated oil bath (23-50 °C). After 3-24 h, the flask was removed from the oil bath and cooled to ambient temperature (23 °C). The reaction was then concentrated, and under positive N2 pressure (to avoid potential air oxidation of the phenolic product) MeOH (3 ml) and saturated aqueous NaHCO3 solution (0.2 ml) were added and the solution was stirred. After 12 h, the reaction was quenched with phosphate buffer (5 ml, pH 7.0) and extracted with EtOAc (10 ml x 33), and the combined organic layers were washed with brine (5 ml), dried over Na2SO4 and concentrated. The crude material was purified by silica-gel column chromatography to afford the desired phenolic product. For full experimental details and characterization of new compounds, see Supplementary Information.

Reference： [1]Pilevar, Afsaneh; Hosseini, Abolfazl; Šekutor, Marina; Hausmann, Heike; Becker, Jonathan; Turke, Kevin; Schreiner, Peter R. [Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 10070 - 10079]
[2]Yuan, Changxia; Liang, Yong; Hernandez, Taylor; Berriochoa, Adrian; Houk, Kendall N.; Siegel, Dionicio [Nature, 2013, vol. 499, # 7457, p. 192 - 196]

35
[ 529-35-1 ]
[ 3717-17-7 ]
[ 1449422-21-2 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 8386 - 8395

36
[ 529-35-1 ]
[ 485-47-2 ]
[ 1416230-82-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With acetic acid at 110℃; for 3h;	31 Example 31 6b,11b-Dihydroxy-1,2,3,4,6b,11b-hexahydro-12-oxa-benzo[4,5]pentaleno[2,1-a]naphthalen-7-one To a solution of ninhydrin (1.00 g, 5.61 mmol) in acetic acid (20 ml) was added 5,6,7,8-tetrahydro-naphthalen-1-ol (0.83 g, 5.61 mmol), followed by heating for 3 hrs at 110° C. After cooling, the precipitate thus formed was filtered to afford the title compound as a white solid. 1.48 g (83%). [0516] mp: 252-254° C. [0517] 1H-NMR (300 MHz, CDCl3) δ 1.72-1.81 (m, 4H, CH2) 2.58-2.67 (m, 4H, CH2) 6.71 (d, J=7.8 Hz, 1H, ArH) 7.21 (d, J=7.8 Hz, 1H, ArH) 7.56 (t, J=8.4 Hz, 1H, ArH) 7.58-7.83 (m, 2H, ArH) 8.02 (d, J=7.5 Hz, 1H, ArH). MS(EI): 308.
83%	With acetic acid at 110℃; for 3h;	31 <EXAMPLE 31> 6b,11b-Dihydroxy-1,2,3,4,6b,11b-hexahydro-12-oxa-benzo[4,5]pentaleno[2,1-a]naphthalen-7-one To a solution of ninhydrin (1.00 g, 5.61 mmol) in acetic acid (20 ml) was added 5,6,7,8-tetrahydro-naphthalen-1-ol (0.83 g, 5.61 mmol), followed by heating for 3 hrs at 110°C. After cooling, the precipitate thus formed was filtered to afford the title compound as a white solid. 1.48 g (83%). mp: 252-254°C. 1H-NMR (300MHz, CDCl3) δ 1.72-1.81(m, 4H, CH2) 2.58-2.67(m, 4H, CH2) 6.71(d, J=7.8Hz, 1H, ArH) 7.21(d, J=7.8Hz, 1H, ArH) 7.56(t, J=8.4Hz, 1H, ArH) 7.58-7.83(m, 2H, ArH) 8.02 (d, J=7.5Hz, 1H, ArH). MS (EI) : 308.

Reference： [1]Current Patent Assignee: KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; KATHOLIEKE UNIVERSITEIT LEUVEN - US2014/114068, 2014, A1 Location in patent: Paragraph 0515-0517
[2]Current Patent Assignee: KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; KATHOLIEKE UNIVERSITEIT LEUVEN - EP2722042, 2014, A2 Location in patent: Paragraph 0076

37
[ 529-35-1 ]
[ 105-36-2 ]
[ 503003-03-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In acetonitrile at 80℃; for 4h;	62.1 Step 1: ethyl 2-((5,6,7 -tetrahydronaphthalen-l-yl)oxy)acetate To a stirred mixture of 5,6,7, 8-tetrahydronaphthalen-l-ol (200 mg, 1.35mmol) in MeCN (5 mL) was added ethyl bromoacetate (269mg ,1.62 mmol) and K2C03 (372mg , 2.70 mmol). The mixture was stirred at 80 °C for 4 hours. The mixture was filtered, the filtrate concentrated to yield the desired product which used directly for the next step without further purification (300 mg, Yield 95%).
95%	With potassium carbonate In acetonitrile at 80℃; for 4h;	62.1 Step 1: ethyl 2-((5,6,7,8-tetrahydronaphthalen-1-yl)oxy)acetate To a stirred mixture of 296 5,6,7,8-tetrahydronaphthalen-1-ol (200 mg, 1.35 mmol) in 40 MeCN (5 mL) was added 41 ethyl bromoacetate (269 mg, 1.62 mmol) and 19 K2CO3 (372 mg, 2.70 mmol). The mixture was stirred at 80° C. for 4 hours. The mixture was filtered, the filtrate concentrated to yield the desired 297 product which used directly for the next step without further purification (300 mg, Yield 95%).

Reference： [1]Current Patent Assignee: EPIZYME, INC. - WO2014/100730, 2014, A1 Location in patent: Paragraph 00329
[2]Current Patent Assignee: EPIZYME, INC. - US2019/83482, 2019, A1 Location in patent: Paragraph 0394-0395

38
[ 28315-93-7 ]
[ 529-35-1 ]

Yield	Reaction Conditions	Operation in experiment
97%		Preparation of 5, 6, 7, 8-tetrahydronaphthalen-1-ol (12). To a solution of 5-hydroxy-1-tetralone 6(1.64g, 10mmol, 1eq) and hydrazine hydrate (1.5g, 30mmol, 3eq) in triethylene glycol was heated to 80oC and stirred for 1.5h until TLC showed the starting material was disappeared. Then KOH (1.68g, 30mmol, 3eq) was added and the temperature was raised to 180oC and stirred for another 7h. The solution was colded to room temperature and added H2O. 3N HCl was added dropwise to the solution until pH was about 8, which was extracted with ethyl acetate three times. The organic layer was combined and washed by brine and dried over Na2SO4. After the solvent was evaporated in vacuum an off-white solid was obtained, 1.44g, yield 97%, which was pure enough for further use.

Reference： [1]Synthetic Communications,2014,vol. 44,p. 2879 - 2885

39
[ 529-35-1 ]
[ 13577-40-7 ]

Reference： [1]Synthetic Communications,2014,vol. 44,p. 2879 - 2885

40
[ 529-35-1 ]
5-bromo-2-chloro-4-methyl-3-nitropyridine [ No CAS ]
5-bromo-4-methyl-3-nitro-2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 4h;	3 5-Bromo-4-methyl-3-nitro-2-(5,6,7,8-tetrahydronaphthalene-l-yloxy)pyridine To a solution of 5,6,7, 8-tetrahydronaphthalen-l-ol (0.148 g, 1.000 mmol) and 5- bromo-2-chloro-4-methyl-3-nitropyridine (0.251 g, 1 mmol) in DMF (Volume: 4 mL) was added potassium carbonate (0.276 g, 2.000 mmol). The mixture was warmed to 100 °C for 4h then cooled and diluted with water. This dark suspension was extracted twice with dichloromethane, and the combined organic extract dried and stripped to afford a dark oil. Chromatography on silica gel (gradient elution with ether-hexanes) afforded 0.2 g(50%) of 5-bromo-4-methyl-3-nitro-2-(5,6,7,8-tetrahydronaphthalen-l-yloxy)pyridine (3 A) as an oily solid. XH NMR (400 MHz, DMSO-d6) δ ppm 8.46(s, 1 H); 7.15(t, 1 H, J = 7.7 Hz); 7.01(d, 1 H, J = 7.5 Hz); 6.93(d, 1H, J = 7.5 Hz); 2.72-2.77(m, 2H); 2.37-2.42(m, 5H); 1.63-1.71(m, 4H). MS(ES): m/z = 365 [M+H]+.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2015/2918, 2015, A1 Location in patent: Page/Page column 66-67

41
[ 529-35-1 ]
[ 908094-04-2 ]
[ 1449422-47-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With [bis(acetoxy)iodo]benzene; water at 70℃;	Preparation of Indazole-4,7-diols 3aa-3da General procedure: A mixture of phenol (1.0 mmol) and PhI(OAc)2 (2.0 mmol) was stirred in water (12mL) at room temperature until the starting material disappeared. The progress of reaction was monitored by TLC (ethyl acetate/hexane). Then diazo (1.5 mmol) was added, then the mixture heated to 70°C. After the intermediate disappeared, saturated Na2S2O3 solution (12 mL) was added, and the mixture stirred at room temperature overnight. The mixture was poured into brine (30 mL) and extracted with dichloromethane (3 × 50 mL). The combined extract was washed with brine (2 × 50mL) and dried over Na2SO4. After evaporation of the solvent under reduced pressure, the residue was chromatographed by silica gel (methanol/dichloromethane 1:100) to obtain the desired products. The correct structures of products were characterized by 1H and 13C NMR and High-resolution mass spectral data.