thian-4-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-3,5-dimethylphenol (0.201 g, 1.00 mmol), tetrahydro-2H-thiopyran-4-ol (0.130 g, 1.10 mmol) and triphenylphosphine (0.341 g, 1.30 mmol) in tetrahydrofuran (5 mL) was added diethyl azodicarboxylate (40% solution in toluene, 0.591 mL, 1.30 mmol), and the mixture was stirred at room temperature for 1.5 hr. Tetrahydro-2H-thiopyran-4-ol (0.0591 g, 0.500 mmol), triphenylphosphine (0.157 g, 0.600 mmol) and diethyl azodicarboxylate (40% solution in toluene, 0.272 mL, 0.600 mmol) were added, and the mixture was further stirred for 1.5 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=0:100-20:80) to give the title compound (0.261 g, yield 86%) as colorless crystals. the mixture was further stirred for 1.5 hr The reaction mixture was concentrated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate:hexane=0:100-20:80)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 200-mL three-necked flask fitted with a stirrer bar coated with Teflon™, were added 5.37 g of 4-hydroxytetrahydrothiopyran (manufactured by SANKYO KASEI Co., Ltd.), 5.08 g of triethyl amine, and 50 mL of dried methylene chloride, and the mixture was stirred under nitrogen atmosphere at 0° C. To the mixture, 5.0 g of methacryloyl chloride was slowly added through a dropping funnel, and the resulted mixture was reacted at 0° C. for 40 minutes, allowed to warm to room temperature, and was further reacted for another 5 hours. After confirming loss of the starting material by a thin layer chromatography (TLC), the reaction solution was poured into a 300-mL separatory funnel, washed with 100 mL of water followed by 100 mL of saturated NaCl solution (brine), and dried with anhydrous sodium sulfate. From the obtained solution, the solvent was removed by an evaporator, to obtain an oily crude product. The crude product was purified by silica gel chromatography using a mixed solution of n-hexane and ethyl acetate to give 5.18 g of tetrahydro-2H-thiopyran-4-yl methacrylate (thiopyran derivative of the following formula 2) (yield: 61.3%). To a 200-mL three-necked flask fitted with a stirrer bar the resulted mixture was reacted at 0° C. for 40 minutes to warm to room temperature was further reacted for another 5 hours the reaction solution was poured into a 300-mL separatory funnel washed with 100 mL of water dried with anhydrous sodium sulfate From the obtained solution, the solvent was removed by an evaporator to obtain an oily crude product The crude product was purified by silica gel chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (0.24 g, 5.98 mmol) was suspended in tetrahydrofuran (19.9 mL) and cooled to 0° C. Tetrahydro-2H-thiopyran-4-ol (0.24 g, 1.99 mmol) was added and the reaction was stirred for 30 minutes. 2-Bromo-6-(bromomethyl)pyridine (Example 190, Step 1) (0.5 g, 1.99 mmol) was added and the reaction was warmed to and maintained at ambient temperature overnight. The reaction was diluted with ethyl acetate, quenched slowly with water, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The crude mixture was purified by silica gel chromatography to yield the title compound. the reaction was warmed to and maintained at ambient temperature overnight quenched slowly with water the layers were separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over magnesium sulfate filtered concentrated The crude mixture was purified by silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from rac-[1-(3,4-dichloro-phenyl)-2-(4-hydroxy-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester and tetrahydro-2H-thiopyran-4-ol in analogy to Example 9c): MS (ISP): 496.2 and 498.1 (M+H)+, 396.1 and 397.9 ((M-Boc)+H)+ (100%).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 3-{2-fluoro-4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (0.50 g, 1.18 mmol), tetrahydro-2H-thiopyran-4-ol (0.15 g, 1.30 mmol) and triphenylphosphine (0.31 g, 1.30 mmol) in tetrahydrofuran (10 mL) was added diethyl azodicarboxylate (40% toluene solution, 0.70 mL, 1.53 mmol) at room temperature with stirring. The reaction mixture was stirred at room temperature for 19 hrs., and an equivalent amount of the aforementioned reagents (tetrahydro-2H-thiopyran-4-ol, triphenylphosphine and diethyl azodicarboxylate) were added. The mixture was further stirred at the same temperature for 6 hrs. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give the title compound (0.53 g, yield 91%) as a yellow oil. The reaction mixture was stirred at room temperature for 19 hrs The mixture was further stirred at the same temperature for 6 hrs The reaction mixture was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 3-{2-fluoro-4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (0.50 g, 1.18 mmol), tetrahydro-2H-thiopyran-4-ol (0.15 g, 1.30 mmol) and triphenylphosphine (0.31 g, 1.30 mmol) in tetrahydrofuran (10 mL) was added diethyl azodicarboxylate (40% toluene solution, 0.70 mL, 1.53 mmol) at room temperature with stirring. The reaction mixture was stirred at room temperature for 19 hrs., and an equivalent amount of the aforementioned reagents (tetrahydro-2H-thiopyran-4-ol, triphenylphosphine and diethyl azodicarboxylate) were added. The mixture was further stirred at the same temperature for 6 hrs. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give the title compound (0.53 g, yield 91%) as a yellow oil. The reaction mixture was stirred at room temperature for 19 hrs The mixture was further stirred at the same temperature for 6 hrs The reaction mixture was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1)