(1R)-1-(3-CHLOROPHENYL)ETHANOL

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

Procedure: A solution of (R)-1-(3-chlorophenyl)ethanol (0.730 g, 4.66 mmol) in dimethylformamide (5 mL) was added to a 0° C. slurry of sodium hydride (0.207 g, 5.18 mmol) in dimethylformamide (5 mL) under nitrogen atmosphere. The reaction mixture was warmed to room temperature, stirred for 3 hour, and then cooled with an ice bath. The cold orange solution was added dropwise to a 0° C. solution of 2,6-difluorobenzonitrile (0.720 g, 5.18 mmol) in dimethylfomamide (5 mL). After the reaction was stirred at ambient temperature for around 18 hours, the reaction was diluted with water and extracted with EA. The organic layer was washed with water and brine, dried over MgSO4, and concentrated in vacuo to a yellow semi-solid. Flash chromatography purification (silica gel, 50% hexane in DCM) afforded the 2-fluoro-5-[(R)-1-(3-chlorophenyl)ethoxy]benzonitrile as a pale yellow oil (0.645 g, 50%). cooled with an ice bath After the reaction was stirred at ambient temperature for around 18 hours extracted with EA The organic layer was washed with water and brine dried over MgSO4 concentrated in vacuo to a yellow semi-solid Flash chromatography purification (silica gel, 50% hexane in DCM)

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

Procedure: To a solution of borane-tetrahydrofuran (0.647 mL, 0.647 mmol, Aldrich, 1 M solution in THF) and (S)-MeCBS (0.647 mL, 0.647 mmol, Aldrich, 1M solution in toluene) was added simultaneously a solution of 3-chloroacetophenone (1.00 g, 6.47 mmol) in anhydrous tetrahydrofuran (2.42 mL) and a solution of borane-tetrahydrofuran (3.24 mL, 3.24 mmol, Aldrich, 1 M solution in THF) over 30 min at ambient temperature. After complete addition, the reaction mixture was stirred for 10 min, quenched slowly at 0° C. with methanol (0.94 mL) and then saturated HCl in ether (0.12 mL). After stirring at 0° C. for 5 min and ambient temperature for 30 min, the solution was concentrated in vacuo to an oil. The oil was twice diluted with benzene and concentrated in vacuo, diluted with ether, and concentrated in vacuo to an oil. The oil was purified by flash chromatography(silica gel, 20% EA in hexane) to give (R)-1-(3-chlorophenyl)ethanol as a clear colorless oil (0.784 g, 78%). Optical rotation in CHCl3 at 20° C. at concentration 0.220 was +40.9° (Literature, Bull. Chem. Soc. Jpn. 1996, 69(4), 1079-1085, optical rotation in CHCl3 at 21° C. at concentration 0.220 was +44°). After complete addition quenched slowly at 0° C. with methanol (0.94 mL) After stirring at 0° C. for 5 min and ambient temperature for 30 min the solution was concentrated in vacuo to an oil The oil was twice diluted with benzene concentrated in vacuo diluted with ether concentrated in vacuo to an oil The oil was purified by flash chromatography(silica gel, 20% EA in hexane)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A ruthenium complex RuCl[(R,R)-Tsdpen] (mesitylene) (2.1 mg, 0.0033 mmol), potassium formate (1.0 g, 12 mmol), formic acid (138 mg, 3 mmol) and 3′-chloroacetophenone (1.55 g, 10 mmol, substrate/catalyst ratio=3000) were set in a 20 mL glass Schlenk-type reaction tube under an argon atmosphere. Methanol (6 mL) was added thereto and stirred at 50° C. for 24 hours to give (R)-1-(3′-chlorophenyl)ethanol at 100% yield and 96.5% ee optical purity.

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

Procedure: A solution of (R)-1-(3-chlorophenyl)ethanol (0.730 g, 4.66 mmol) in dimethylformamide (5 mL) was added to a 0° C. slurry of sodium hydride (0.207 g, 5.18 mmol) in dimethylformamide (5 mL) under nitrogen atmosphere. The reaction mixture was warmed to room temperature, stirred for 3 hour, and then cooled with an ice bath. The cold orange solution was added dropwise to a 0° C. solution of 2,6-difluorobenzonitrile (0.720 g, 5.18 mmol) in dimethylfomamide (5 mL). After the reaction was stirred at ambient temperature for around 18 hours, the reaction was diluted with water and extracted with EA. The organic layer was washed with water and brine, dried over MgSO4, and concentrated in vacuo to a yellow semi-solid. Flash chromatography purification (silica gel, 50% hexane in DCM) afforded the 2-fluoro-5-[(R)-1-(3-chlorophenyl)ethoxy]benzonitrile as a pale yellow oil (0.645 g, 50%). cooled with an ice bath After the reaction was stirred at ambient temperature for around 18 hours extracted with EA The organic layer was washed with water and brine dried over MgSO4 concentrated in vacuo to a yellow semi-solid Flash chromatography purification (silica gel, 50% hexane in DCM)

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

Procedure: To a solution of borane-tetrahydrofuran (0.647 mL, 0.647 mmol, Aldrich, 1 M solution in THF) and (S)-MeCBS (0.647 mL, 0.647 mmol, Aldrich, 1M solution in toluene) was added simultaneously a solution of 3-chloroacetophenone (1.00 g, 6.47 mmol) in anhydrous tetrahydrofuran (2.42 mL) and a solution of borane-tetrahydrofuran (3.24 mL, 3.24 mmol, Aldrich, 1 M solution in THF) over 30 min at ambient temperature. After complete addition, the reaction mixture was stirred for 10 min, quenched slowly at 0° C. with methanol (0.94 mL) and then saturated HCl in ether (0.12 mL). After stirring at 0° C. for 5 min and ambient temperature for 30 min, the solution was concentrated in vacuo to an oil. The oil was twice diluted with benzene and concentrated in vacuo, diluted with ether, and concentrated in vacuo to an oil. The oil was purified by flash chromatography (silica gel, 20% EA in hexane) to give (R)-1-(3-chlorophenyl)ethanol as a clear colorless oil (0.784 g, 78%). Optical rotation in CHCl3 at 20° C. at concentration 0.220 was +40.90 (Literature, Bull. Chem. Soc. Jpn. 1996, 69(4), 1079-1085, optical rotation in CHCl3 at 21° C. at concentration 0.220 was +44°). After complete addition quenched slowly at 0° C. with methanol (0.94 mL) After stirring at 0° C. for 5 min and ambient temperature for 30 min the solution was concentrated in vacuo to an oil The oil was twice diluted with benzene concentrated in vacuo diluted with ether concentrated in vacuo to an oil The oil was purified by flash chromatography (silica gel, 20% EA in hexane)