Name: 7335-12-8|Cis-4-Phenylcyclohexan-1-ol|95%
Brand: Ambeed
SKU: A723232
Price: 64.0 USD
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1
[ 7335-12-8 ]
trans-4-phenylcyclohexanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium at 200℃;

Reference： [1]Ungnade [Journal of Organic Chemistry, 1948, vol. 13, p. 361,364]

2
[ 827-52-1 ]
[ 1589-60-2 ]
[ 771-98-2 ]
[ 942-92-7 ]
[ 4894-75-1 ]
[ 5437-46-7 ]
[ 7335-12-8 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1980,vol. 16,p. 654 - 659
Zhurnal Organicheskoi Khimii,1980,vol. 16,p. 745 - 751

3
[ 92-69-3 ]
trans-4-phenylcyclohexanol [ No CAS ]
[ 7335-12-8 ]
[ 7335-42-4 ]
[ 7335-11-7 ]
[ 1131-60-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 11% 2: 11% 3: 34% 4: 8% 5: 6%	With hydrogen In ethanol at 50℃; for 5h; other biphenyls; other solvent, other catalysts;

Reference： [1]Minabe, Masahiro; Watanabe, Kousuke; Ayabe, Yooichi; Yoshida, Masaaki; Toda, Takashi [Journal of Organic Chemistry, 1987, vol. 52, # 9, p. 1745 - 1748]

4
[ 75-15-0 ]
[ 7335-12-8 ]
[ 74-88-4 ]
O-(cis-4-phenylcyclohexyl) S-methyl dithiocarbonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride Yield given. Multistep reaction;

Reference： [1]Crich, David; Beckwith, Athelstan L. J.; Chen, Chen; Yao, Qingwei; Davison, Ian G. E.; Longmore, Robert W.; De Parrodi, Cecilia Anaya; Quintero-Cortes, Leticia; Sandoval-Ramirez, Jésus [Journal of the American Chemical Society, 1995, vol. 117, # 34, p. 8757 - 8768]

5
2-cis-Brom-4-cis-phenylcyclohexanol [ No CAS ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; hydrogen In ethanol

Reference： [1]Curtin,D.Y.; Harder,R.J. [Journal of the American Chemical Society, 1960, vol. 82, p. 2357 - 2368]

6
[ 827-52-1 ]
[ 5437-46-7 ]
[ 7335-12-8 ]
[ 22147-17-7 ]

Reference： [1]Chemical Communications,1996,p. 357 - 358

7
[ 827-52-1 ]
[ 37982-27-7 ]
[ 5437-46-7 ]
[ 7335-12-8 ]

Reference： [1]Chemical Communications,1996,p. 2413 - 2414

8
[ 827-52-1 ]
[ 5437-46-7 ]
[ 7335-12-8 ]

Reference： [1]Chemical Communications,1996,p. 2413 - 2414
[2]Chemical Communications,1996,p. 2413 - 2414

9
[ 4894-75-1 ]
trans-4-phenylcyclohexanol [ No CAS ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 77% 2: 9%	With lithium aluminium tetrahydride In diethyl ether at 20℃; for 0.5h; Inert atmosphere;
60%	With lithium aluminium tetrahydride In diethyl ether for 2h; Heating;
1: 22% 2: 37%	With ammonium hydroxide; titanium(III) chloride In methanol at 0 - 20℃; for 0.0833333h;

1: 28.4% 2: 10.4%	With sodium tetrahydroborate In ethanol at 25℃; for 1h;
	With lithium aluminium tetrahydride In tetrahydrofuran
	With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 60℃; Title compound not separated from byproducts;
	With potassium hydroxide; tris(triphenylphosphine)ruthenium(II) chloride; hydrogen; ethylenediamine In isopropyl alcohol at 28℃; for 1h; Title compound not separated from byproducts;
33.333 % de	With HN(CH₂CH₂C₃H₃N₂Mes)2Cl₂; potassium <i>tert</i>-butylate; hydrogen; cobalt(II) chloride In tetrahydrofuran at 60℃; for 16h; Autoclave; Overall yield = 98 %; stereoselective reaction;	4-tert-butylcyclohexanone 1au was reduced according to the abovementioned hydrogenation protocol in 2 mmol scale. The reaction was conducted by using 2mol% L1d/CoCl2 and 10 mol% tBuOK in 2 mL THF under 50 bar H2, at 60 for 16 h. Afterreaction, the mixture was dried under vacuum and the resulted raw product was further purifiedby flash column chromatography on silica gel using PE : EA = 25:1 as eluent to afford thedesired alcohol 2au in 99% yield.
77.778 % de	With C₁₂H₂₁N₅⁽²⁺⁾*2Cl^(1-); potassium <i>tert</i>-butylate; hydrogen; cobalt(II) chloride In tetrahydrofuran at 60℃; for 16h; Autoclave; Overall yield = 99 %Chromat.; stereoselective reaction;	4-tert-butylcyclohexanone 1au was reduced according to the abovementioned hydrogenation protocol in 2 mmol scale. The reaction was conducted by using 2mol% L1d/CoCl2 and 10 mol% tBuOK in 2 mL THF under 50 bar H2, at 60 for 16 h. Afterreaction, the mixture was dried under vacuum and the resulted raw product was further purifiedby flash column chromatography on silica gel using PE : EA = 25:1 as eluent to afford thedesired alcohol 2au in 99% yield.
66.667 % de	With bis(1,5-cyclooctadiene)diiridium(I) dichloride; ethanol; hydrogen; C₃₁H₃₀FeNOP; isopropyl alcohol; lithium tert-butoxide at 20℃; for 12h; Overall yield = > 99 percent;	18 Example 18 uses Ir-(S_FC)-L1 catalyst for selective hydrogenation of 4-phenylcyclohexanone In an argon glove box, the ligand (SFC)-L1(5.5mg,0.0105mmol) and [Ir(COD)Cl]2(3.4mg, 0.005mmol) was added 2mL vials inside, withIPrOH (1 mL) and dissolved at room temperature stirred for 2h.The raw material 4-phenylcyclohexanone (1 mmol) was put into a 4 mL hydrogenation flask.Then add 0.1 mL of the in-situ complexed catalyst solution and 1.6 mg oftBuOLi solid powderto the hydrogenation flask, and finally add 1 mL of EtOH to dissolve the reactants, then put the reaction flask into the hydrogenation kettle, and replace the kettle body with hydrogen for three times. Charge 5bar H2, React for 12h at room temperature.After the reaction is completed, the hydrogen is released carefully, the solvent is spin-dried under reduced pressure, and the hydrogenated product 4-phenylcyclohexanol is purified by silica gel column, white solid, >99% conversion, >99% yield, cis/trans=5:1.Cis-4-phenylcyclohexanol;
50 % de	Stage #1: 1-phenyl-4-cyclohexanone With potassium <i>tert</i>-butylate; C₃₆H₂₈FeMnN₂O₃P⁽¹⁺⁾*Br^(1-) In ethanol at 20℃; for 0.0833333h; Glovebox; Stage #2: With hydrogen In ethanol at 50℃; for 16h; Glovebox; Autoclave;	21 Example 21 Asymmetric hydrogenation of phenylcyclohexanone with Mn-PNN catalyst In the glove box, add Mn cat.1 catalyst (1.5mg, 0.002mmol) and substrate 4-phenylcyclohexanone (174mg, 1mmol) into a 5mL clear glass vial, then potassium tert-butoxide (2.2 mg, 0.02 mmol) and absolute ethanol (3 mL) were added, and the mixture was stirred at room temperature for 5 min. Finally, the hydrogenation bottle was put into the autoclave, the hydrogen was replaced three times and then filled with 30 bar H2, and reacted at 50°C for 16h. After the reaction is completed, the hydrogen is released carefully, the solvent is spin-dried under reduced pressure, and the hydrogenated product alcohol is obtained through silica gel column purification, which is a white solid. The reaction is determined by HPLC, >99% yield, cis/trans=3:1.

Reference： [1]Povie, Guillaume; Tran, Anh-Tuan; Bonnaffe, David; Habegger, Jacqueline; Hu, Zhaoyu; Le Narvor, Christine; Renaud, Philippe [Angewandte Chemie - International Edition, 2014, vol. 53, # 15, p. 3894 - 3898][Angew. Chem., 2014, vol. 126, # 15, p. 3975 - 3979,5]
[2]Imboden, Christoph; Villar, Felix; Renaud, Philippe [Organic Letters, 1999, vol. 1, # 6, p. 873 - 875]
[3]Clerici, Angelo; Pastori, Nadia; Porta, Ombretta [European Journal of Organic Chemistry, 2001, # 12, p. 2235 - 2243]
[4]Penning, Thomas D.; Chandrakumar, Nizal S.; Chen, Barbara B.; Chen, Helen Y.; Desai, Bipin N.; Djuric, Stevan W.; Docter, Stephen H.; Gasiecki, Alan F.; Haack, Richard A.; Miyashiro, Julie M.; Russell, Mark A.; Yu, Stella S.; Corley, David G.; Durley, Richard C.; Kilpatrick, Brian F.; Parnas, Barry L.; Askonas, Leslie J.; Gierse, James K.; Harding, Elizabeth I.; Highkin, Maureen K.; Kachur, James F.; Kim, Suzanne H.; Krivi, Gwen G.; Villani-Price, Doreen; Pyla, E. Yvonne; Smith, Walter G.; Ghoreishi-Haack, Nayereh S. [Journal of Medicinal Chemistry, 2000, vol. 43, # 4, p. 721 - 735]
[5]Maeda, Hatsuo; Koide, Takashi; Matsumoto, Sayaka; Ohmori, Hidenobu [Chemical and Pharmaceutical Bulletin, 1996, vol. 44, # 8, p. 1480 - 1483]
[6]Doucet, Henri; Ohkuma, Takeshi; Murata, Kunihiko; Yokozawa, Tohru; Kozawa, Masami; Katayama, Eiji; England, Anthony F.; Ikariya, Takao; Noyori, Ryoji [Angewandte Chemie - International Edition, 1998, vol. 37, # 12, p. 1703 - 1707]
[7]Ohkuma, Takeshi; Ooka, Hirohito; Yamakawa, Masashi; Ikariya, Takao; Noyori, Ryoji [Journal of Organic Chemistry, 1996, vol. 61, # 15, p. 4872 - 4873]
[8]Zhong, Rui; Wei, Zeyuan; Zhang, Wei; Liu, Shun; Liu, Qiang [Chem, 2019, vol. 5, # 6, p. 1552 - 1566]
[9]Zhong, Rui; Wei, Zeyuan; Zhang, Wei; Liu, Shun; Liu, Qiang [Chem, 2019, vol. 5, # 6, p. 1552 - 1566]
[10]Current Patent Assignee: LUOYANG NORMAL UNIVERSITY - CN112961194, 2021, A Location in patent: Paragraph 0111-0113
[11]Current Patent Assignee: LUOYANG NORMAL UNIVERSITY - CN113024615, 2021, A Location in patent: Paragraph 0121-0122

10
[ 7335-12-8 ]
[ 603-35-0 ]
C₃₀H₃₀OP⁽¹⁺⁾*BF₄^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphonium tetrafluoroborate In dichloromethane Ambient temperature; electrochemical reaction;

Reference： [1]Maeda, Hatsuo; Koide, Takashi; Matsumoto, Sayaka; Ohmori, Hidenobu [Chemical and Pharmaceutical Bulletin, 1996, vol. 44, # 8, p. 1480 - 1483]

11
[ 827-52-1 ]
[ 5437-46-7 ]
[ 7335-12-8 ]
[ 49673-74-7 ]

Reference： [1]Bioorganic Chemistry,1999,vol. 27,p. 81 - 90

12
[ 4894-75-1 ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
22%	With L-Selectride In tetrahydrofuran for 0.5h; Under N₂;	1 Preparation of trans-1-Amino-4-phenylcyclohexane [0167] Preparation of trans-1-Amino-4-phenylcyclohexane 5 [CHEMMOL-00011] [0168] Step 1: To an ice-cold, stirred solution of 4-phenylcyclohexanone 1 (25.0 g, 140 mmol) in THF (200 mL), under an N2 atmosphere, was added L-selectride (172 mL of a 1.0 M solution in THF, 170 mmol) dropwise over 15 minutes. After 0.5 hours of stirring, the reaction mixture was quenched by the careful addition of H2O. The reaction mixture was partitioned between EtOAc (800 mL) and 2N HCl (500 mL). The organic layer was washed with saturated NaHCO3 (500 mL), and saturated NaCl (500 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (alumina, THF) gave alcohol 2 (5.4 g, 22%): 1H NMR (300 MHz, CDCl3) ? 7.39-7.14 (m, 5H), 4.64-4.54 (m, 1H), 2.65-2.51 (m, 1H), 2.09-1.82 (m, 4H), 1.79-1.58 (m, 4H).
	Multi-step reaction with 4 steps 1: (i) NaNH₂, liq. NH₃, Fe(NO₃)3, (ii) /BRN= 1900390/ 2: Br₂, aq. NaOAc, KBr 3: LiAlH₄ 4: H₂, KOH / Pd / aq. ethanol / 1034.3 Torr
93 %Chromat.	With C₃₄H₄₉N₅⁽²⁺⁾*2Cl^(1-); potassium <i>tert</i>-butylate; hydrogen; cobalt(II) chloride In tetrahydrofuran at 60℃; for 16h; Autoclave; stereoselective reaction;	General procedure for Hydrogenation of Ketones General procedure: 4-tert-butylcyclohexanone 1au was reduced according to the abovementioned hydrogenation protocol in 2 mmol scale. The reaction was conducted by using 2mol% L1d/CoCl2 and 10 mol% tBuOK in 2 mL THF under 50 bar H2, at 60 for 16 h. Afterreaction, the mixture was dried under vacuum and the resulted raw product was further purifiedby flash column chromatography on silica gel using PE : EA = 25:1 as eluent to afford thedesired alcohol 2au in 99% yield.

	With L-Selectride In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;	405 General procedure: To a solution of Compound 393E (820 mg, 2.8 mmol) in anhydrous THF (20 mL) was dropped L-Selectride solution of (1 M in THF, 4.2 mL, 4.2 mmol) at -78 °C under nitrogen and stirred at -78 °C for 2 hours. The reaction mixture was quenched with saturated aqueous NH4CI solution (30 mL), stirred at room temperature for 0.5 hour, and extracted with EtOAc (50 mL x 3). The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to furnish Compounds 393F-1 and 393F-2. Compounds 393F-1: LC-MS (ESI) m/z: 277 [M-OH]+; 1H-NMR (CDCb, 400 MHz): d (ppm) 1.57-1.61 (m, 2H), 1.68-1.73 (m, 2H), 1.82-1.93 (m, 4H), 2.87-2.95 (m, 1H), 4.16-4.17 (m, 1H), 7.14-7.19 (m, 2H), 7.35-7.36 (m, 1H). Compounds 393F-2: LC-MS (ESI) m/z: 277 [M-OH]+; -NMR (CDCb, 400 MHz): d (ppm) 1.34-1.42 (m, 4H), 1.78-1.82 (m, 2H), 2.03-2.05 (m, 2H), 2.78-2.81 (m, 1H), 3.59-3.63 (m, 1H), 7.08-7.17 (m, 2H), 7.18-7.19 (m, 1H).
	With L-Selectride In tetrahydrofuran at -78 - 0℃; for 5.33333h;	(CIS)-4-phenylcyclohexanol To a mixture of 4-phenylcyclohexanone (10.50 g, 60.3 mmol) in THF (201 mL) at -78° C. was added L-Selectride (102 mL, 102 mmol) in THF over 20 min. The mixture stirred at -78° C. for 3 hours before warming to 0° C. and stirring for an additional 2 hours. The reaction was quenched with a saturated solution of NH4Cl (200 mL), extracted with EtOAc (250 mL×3), dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica (2% to 60% EtOAc/hexanes) to afford the title compound. MS: 199.9 (M+23).
	With L-Selectride In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;	405 General procedure: To a solution of Compound 393E (820 mg, 2.8 mmol) in anhydrous THF (20 mL) was dropped L-Selectride solution of (1 M in THF, 4.2 mL, 4.2 mmol) at -78 oC under nitrogen and stirred at -78 oC for 2 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution (30 mL), stirred at room temperature for 0.5 hour, and extracted with EtOAc (50 mL x 3). The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to furnish Compounds 393F-1 and 393F-2. Compounds 393F-1: LC-MS (ESI) m/z: 277 [M-OH]+; 1H-NMR (CDCl3, 400 MHz): d (ppm) 1.57-1.61 (m, 2H), 1.68-1.73 (m, 2H), 1.82-1.93 (m, 4H), 2.87-2.95 (m, 1H), 4.16-4.17 (m, 1H), 7.14-7.19 (m, 2H), 7.35-7.36 (m, 1H). Compounds 393F-2: LC-MS (ESI) m/z: 277 [M-OH]+; 1H-NMR (CDCl3, 400 MHz): d (ppm) 1.34-1.42 (m, 4H), 1.78-1.82 (m, 2H), 2.03-2.05 (m, 2H), 2.78-2.81 (m, 1H), 3.59-3.63 (m, 1H), 7.08-7.17 (m, 2H), 7.18-7.19 (m, 1H).

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/225164, 2003, A1 Location in patent: Page 9
[2]Curtin,D.Y.; Harder,R.J. [Journal of the American Chemical Society, 1960, vol. 82, p. 2357 - 2368]
[3]Zhong, Rui; Wei, Zeyuan; Zhang, Wei; Liu, Shun; Liu, Qiang [Chem, 2019, vol. 5, # 6, p. 1552 - 1566]
[4]Current Patent Assignee: BIOMARIN PHARMACEUTICAL INC - WO2019/133770, 2019, A2 Location in patent: Paragraph 001936; 001937; 001939; 001978; 001979; 001980
[5]Current Patent Assignee: MERCK & CO INC - US2020/255403, 2020, A1 Location in patent: Paragraph 0306; 0307
[6]Current Patent Assignee: BIOMARIN PHARMACEUTICAL INC; BIOMARIN PHARM INC - WO2020/257487, 2020, A1 Location in patent: Paragraph 001894; 001896; 001936; 001937

13
[ 91909-96-5 ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Br₂, aq. NaOAc, KBr 2: LiAlH₄ 3: H₂, KOH / Pd / aq. ethanol / 1034.3 Torr

Reference： [1]Curtin,D.Y.; Harder,R.J. [Journal of the American Chemical Society, 1960, vol. 82, p. 2357 - 2368]

14
cis-2-Brom-4-phenylcyclohexanon [ No CAS ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: LiAlH₄ 2: H₂, KOH / Pd / aq. ethanol / 1034.3 Torr

Reference： [1]Curtin,D.Y.; Harder,R.J. [Journal of the American Chemical Society, 1960, vol. 82, p. 2357 - 2368]

15
[ 7335-12-8 ]
[ 124-63-0 ]
[ 376634-08-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine In tetrahydrofuran for 1h; Under N₂;	2 Preparation of trans-1-Amino-4-phenylcyclohexane [0169] Step 2: To an ice-cold, stirred solution of alcohol 2 (5.4 g, 31 mmol) in TBF (200 mL), under an N2 atmosphere, was added Et3N (6.5 mL, 47 mmol) followed by methanesulfonyl chloride (2.9 mL, 37 mmol). After 1 hour, the reaction mixture was partitioned between EtOAc (500 mL) and 2N HCl (500 mL). The organic layer was washed with H2O (500 mL), saturated NaHCO3 (500 mL) and saturated NaCl, dried (Na2SO4), and filtered. Concentration under reduced pressure gave mesylate 3 (5.5 g, 70%), which was used without further purification: 1H NMR (500 MHz, CDCl3) ? 7.31-7.18 (m, 5H), 5.06-5.03 (m, 1H), 3.03 (s, 3H), 2.65-2.54 (m, 1H), 2.25-2.17 (m, 2H), 1.90-1.65 (m, 6H).

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/225164, 2003, A1 Location in patent: Page 9

16
[ 7335-12-8 ]
[ 1125-62-8 ]
4-(cis-4-Phenyl-cyclohexyloxy)-5,6,7,8-tetrahydroquinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With NaH; In tetrahydrofuran;	4-(cis-4-Phenyl-cyclohexyloxy)-5,6,7,8-tetrahydroquinazoline 0.5 g (16.7 mmol) of 80% NaH was added in portions to a solution of 1.85 g (105 mmol) of cis-4-phenylcyclohexanol in 30 ml of absolute THF. After this, the mixture was heated for 1 hour at 50 C., and 1.5 g (8.75 mmol) of <strong>[1125-62-8]4-chloro-5,6,7,8-tetrahydroquinazoline</strong>, dissolved in 15 ml of absolute THF, were added dropwise. The reaction mixture was subsequently refluxed for 2 hours. After the mixture had cooled to room temperature, it was poured into saturated NH4 Cl solution and this was extracted with ether, and the combined organic phase was dried over MgSO4. The solvent was evaporated in vacuo, and the residue (2.7 g) was purified by flash chromatography over silica gel, using n-hexane/ethyl acetate (2:1). Concentration gave 1.5 g (50.2% of theory), colorless crystals, m.p. 109 C. STR12

Reference： [1]Patent: US5571815,1996,A

17
[ 7335-12-8 ]
4-methoxy-3-(trans-4-phenylcyclohexyloxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37.5%		78.1 (1) (1) Synthesis of 4-methoxy-3-(trans-4-phenylcyclohexyloxy)benzaldehyde According to the same procedure as in Example 4(1), using cis-1-hydroxy-4-phenylcyclohexane instead of cyclopropylcarbinol, 4-methoxy-3-(trans-4-phenylcyclohexyloxy)benzaldehyde (yield 37.5%) was obtained as a colorless solid. 1H-NMR (400 MHz, CDCl3) δ1.59-1.76 (4H, m), 2.01-2.04 (2H, m), 2.30-2.33 (2H, m), 2.60 (1H, m), 3.96 (3H, s), 4.35-4.41 (1H, m), 7.00 (1H, d, J=7.81 Hz), 7.19-7.33 (5H, m), 7.46-7.48 (2H, m), 9.86 (1H, s)
37.5%		33.1 (1) (1) 4-methoxy-3-(trans-4-phenylcyclohexyloxy)benzaldehyde According to the same procedure as used in Example 4(1), using cis-1-hydroxy-4-phenylcyclohexane instead of phenethyl alcohol, 4-methoxy-3-(trans-4-phenylcyclohexyloxy)benzaldehyde (yield 37.5%) was obtained as a colorless solid. 1H-NMR (400 MHz, CDCl3) δ 1.59-1.76 (4H, m), 2.01-2.04 (2H, m), 2.30-2.33 (2H, m), 2.60 (1H, m), 3.96 (3H, s), 4.35-4.41 (1H, m), 7.00 (1H, d, J=7.81 Hz), 7.19-7.33 (5H, m), 7.46-7.48 (2H, m), 9.86 (1H, s).

Reference： [1]Current Patent Assignee: KOWA COMPANY, LTD. - US6251897, 2001, B1
[2]Current Patent Assignee: KOWA COMPANY, LTD. - US6265402, 2001, B1

18
[ 1093198-52-7 ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With (triphenylphosphine)gold(I) chloride; silver trifluoromethanesulfonate In ethanol; benzene at 20℃; for 1h;

Reference： [1]Location in patent: scheme or table Umetsu, Kazuteru; Asao, Naoki [Tetrahedron Letters, 2008, vol. 49, # 49, p. 7046 - 7049]

19
[ 7335-12-8 ]
2-(2-Methoxy-phenylethynyl)-benzoic acid [ No CAS ]
[ 1093198-52-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 2-(2-Methoxy-phenylethynyl)-benzoic acid With oxalyl dichloride Stage #2: cis-4-phenylcyclohexanol With pyridine

Reference： [1]Location in patent: scheme or table Umetsu, Kazuteru; Asao, Naoki [Tetrahedron Letters, 2008, vol. 49, # 49, p. 7046 - 7049]

20
[ 29538-77-0 ]
[ 100-59-4 ]
trans-4-phenylcyclohexanol [ No CAS ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: trans-4-hydroxycyclohexyl chloride; phenylmagnesium chloride With aluminum (III) chloride In tetrahydrofuran at 0 - 20℃; for 1.5h; Stage #2: With dichloro(1,2-{bis[3,5-bis(trimethylsilyl)pheny]phosphino-κP}benzene)iron(II) In tetrahydrofuran at 80℃; for 12h; Stage #3: With hydrogenchloride In tetrahydrofuran; water at 0 - 20℃; for 3h; optical yield given as %de; diastereoselective reaction;

Reference： [1]Kawamura, Shintaro; Kawabata, Tatsuya; Ishizuka, Kentaro; Nakamura, Masaharu [Chemical Communications, 2012, vol. 48, # 75, p. 9376 - 9378]

21
[ 92-69-3 ]
trans-4-phenylcyclohexanol [ No CAS ]
[ 7335-12-8 ]
[ 1131-60-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen In tetrahydrofuran at 99.84℃; for 1h; Autoclave; Sealed tube; regioselective reaction;

Reference： [1]Liu, Chengyun; Lu, Lianhai; Rong, Zeming; Liang, Changhai; Wang, Yue; Qu, Qingping [Catalysis Letters, 2012, vol. 142, # 11, p. 1321 - 1329]

22
[ 1466-74-6 ]
trans-4-phenylcyclohexanol [ No CAS ]
[ 7335-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4‐phenylcyclohexan‐1‐carbaldehyde With Co(3-Me-5-MeO-salen) In acetonitrile at -20 - 20℃; for 0.166667h; Inert atmosphere; Stage #2: With dihydrogen peroxide In water; acetonitrile at -20℃; for 24h; Inert atmosphere; Overall yield = 75 %; Further stages;

Reference： [1]Watanabe, Eiichi; Kaiho, Atsushi; Kusama, Hiroyuki; Iwasawa, Nobuharu [Journal of the American Chemical Society, 2013, vol. 135, # 32, p. 11744 - 11747]

23
[ 7335-12-8 ]
[ 106-95-6 ]
[ 1624284-58-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: cis-4-phenylcyclohexanol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 40℃; for 0.5h; Inert atmosphere; Stage #2: allyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Inert atmosphere;
22 g	Stage #1: cis-4-phenylcyclohexanol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran at 60℃; for 12h;	1.A A) (cis-4-(allyloxy)cyclohexyl)benzene A) (cis-4-(allyloxy)cyclohexyl)benzene To a mixture of cis-4-phenylcyclohexanol (20.0 g) and THF (300 ml) was added 60% sodium hydride (5.90 g) at 0° C. The mixture was stirred under nitrogen atmosphere, at 0° C. for 30 min, and allyl bromide (20.6 g) was added thereto. The mixture was stirred under nitrogen atmosphere, at 60° C. for 12 hr. The mixture was poured into water, and extracted with ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (22.0 g). 1H NMR (400 MHz, CDCl3) δ 1.51-1.71 (4H, m), 1.84-1.96 (2H, m), 2.05-2.11 (2H, m), 2.53-2.61 (1H, m), 3.69-3.73 (1H, m), 4.02-4.05 (2H, m), 5.21 (1H, dd, J=10.4, 1.6 Hz), 5.21 (1H, dd, J=16.8, 1.6 Hz), 5.96-6.05 (1H, m), 7.20-7.35 (5H, m).

Reference： [1]Povie, Guillaume; Tran, Anh-Tuan; Bonnaffe, David; Habegger, Jacqueline; Hu, Zhaoyu; Le Narvor, Christine; Renaud, Philippe [Angewandte Chemie - International Edition, 2014, vol. 53, # 15, p. 3894 - 3898][Angew. Chem., 2014, vol. 126, # 15, p. 3975 - 3979,5]
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2020/385346, 2020, A1 Location in patent: Paragraph 0350-0351

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Yield	Reaction Conditions	Operation in experiment
13%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 16h;	17 Example 17: l-((4-methyl-2-((trans-4-phenylcyclohexyl)oxy)naphthalen-l- yl)methyl)piperidine-4-carboxylic acid Example 17: l-((4-methyl-2-((trans-4-phenylcyclohexyl)oxy)naphthalen-l- yl)methyl)piperidine-4-carboxylic acid Using the same condition as that of ethyl l-((2-(cyclohexyloxy)-4- methylnaphthalen- 1 -yl)methyl)piperidine-4-carboxylate, ethyl 1 -((4-methyl-2-((trans-4- phenylcyclohexyl)oxy)naphthalen-l-yl)methyl)piperidine-4-carboxylate was obtained as a yellow oil (40 mg, 13% yield). LCMS m/z 486.3 [M+H] +. Hydrolysis following standard condition gave the title compound as a white solid (23 mg, 61% yield). LCMS m/z 458.3 [M+H] +; 1H NMR (400 MHz, CDC13) δ: 8.28 (d, / = 8.8 Hz, 1H), 7.91 (d, / = 8.4 Hz, 1H), 7.49 (t, / = 7.6 Hz, 1H), 7.39-7.29 (m, 3H), 7.24- 7.19 (m, 3H), 7.15 (s, 1H), 4.58 (s, 2H), 4.47-4.41 (m, 1H), 3.45-3.42 (m, 2H), 2.71 (s, 3H), 2.64-2.48 (m, 3H), 2.26-2.13 (m, 3H), 2.03-1.86 (m, 6H), 1.70-1.51 (m, 4H).

Reference： [1]Current Patent Assignee: BIOGEN IDEC INC. - WO2014/120764, 2014, A1 Location in patent: Page/Page column 54

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Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: triethylamine / tetrahydrofuran / 1 h / Under N₂ 2: sodium azide; tetrabutylammonium hydrogen sulfate / dimethyl sulfoxide / 60 h / 40 - 45 °C 3: hydrogen; acetic acid / palladium 10% on activated carbon / methanol / 3 h / 2585.81 Torr 4: benzotriazol-1-ol / 1,2-dichloro-ethane; N,N-dimethyl-formamide / Under N₂ 5: diisobutylaluminium hydride / toluene / Under N₂; Heating / reflux