(1S)-1-(3-chlorophenyl)ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of (S)-1-(3-chlorophenyl)ethanol (20.4 g, 130.26 mmol) in dimethylformamide was added to a cooled (0° C.) slurry of sodium hydride (5.73 g, 143.29 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, stirred for 1 hour. Again, cooled (0° C.), then a solution of 2,6-difluorobenzonitrile (19.93 g, 143.29 mmol) in dimethylfomamide was added, stirred overnight at room temperature. The reaction mixture was poured on crushed ice-water, stirred, extracted with ether, dried, filtered and concentrated to afford 30.0 g of 2-fluoro-5-[(S)-1-(3-chlorophenyl)ethoxy]benzonitrile. Again, cooled (0° C.) stirred overnight at room temperature The reaction mixture was poured stirred extracted with ether dried filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of borane-tetrahydrofuran (77.6 mL, 77.62 mmol, Aldrich, 1 M solution in THF) and (R)-MeCBS (12.9 mL, 12.9 mmol, Aldrich, 1M solution in toluene) was added a solution of 3-chloroacetophenone (20.0 g, 129.37 mmol) in anhydrous tetrahydrofuran slowly over 30 min at room temperature. After complete addition, the reaction mixture was stirred for 10 min, quenched with 2N hydrochloric acid over 30 min. The reaction mixture was extracted with ether, dried, filtered and concentrated to afford 20.8 g of (S)-1-(3-chlorophenyl)ethanol as a viscous liquid. After complete addition quenched with 2N hydrochloric acid over 30 min The reaction mixture was extracted with ether dried filtered concentrated

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A ruthenium complex RuCl[(S,S)-BnSO2dpen] (mesitylene) (1.2 mg, 0.002 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=5000) 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 (S)-1-(3′-chlorophenyl)ethanol at 85% yield and 96.5% ee optical purity.

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 3-ethoxy-3-(4-hydroxyphenyl)propionate (100 mg, 0.420 mmol) produced in Example 1 (1C) and (1S)-1-(3-chlorophenyl)ethanol (99 mg, 0.630 mmol) were dissolved in tetrahydrofuran (10 mL), and triphenylphosphine (178 mg, 0.680 mmol) and a 40% diethyl azodicarboxylate toluene solution (309 μL, 0.680 mmol) were added thereto at room temperature, and then, the resulting mixture was stirred under a nitrogen atmosphere at 50° C. for 4 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 95:5 (v/v)), whereby the objective title compound was obtained as a yellow oily substance (142 mg, yield: 90%). After the reaction solution was cooled to room temperature the solvent was distilled off under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 95:5 (v/v)), whereby the objective title compound was obtained as a yellow oily substance (142 mg, yield: 90%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of (S)-1-(3-chlorophenyl)ethanol (20.4 g, 130.26 mmol) in dimethylformamide was added to a cooled (0° C.) slurry of sodium hydride (5.73 g, 143.29 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, stirred for 1 hour. Again, cooled (0° C.), then a solution of 2,6-difluorobenzonitrile (19.93 g, 143.29 mmol) in dimethylfomamide was added, stirred overnight at room temperature. The reaction mixture was poured on crushed ice-water, stirred, extracted with ether, dried, filtered and concentrated to afford 30.0 g of 2-fluoro-5-[(S)-1-(3-chlorophenyl)ethoxy]benzonitrile. Again, cooled (0° C.) stirred overnight at room temperature The reaction mixture was poured stirred extracted with ether dried filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of borane-tetrahydrofuran (77.6 mL, 77.62 mmol, Aldrich, 1 M solution in THF) and (R)-MeCBS (12.9 mL, 12.9 mmol, Aldrich, 1M solution in toluene) was added a solution of 3-chloroacetophenone (20.0 g, 129.37 mmol) in anhydrous tetrahydrofuran slowly over 30 min at room temperature. After complete addition, the reaction mixture was stirred for 10 min, quenched with 2N hydrochloric acid over 30 min. The reaction mixture was extracted with ether, dried, filtered and concentrated to afford 20.8 g of (S)-1-(3-chlorophenyl)ethanol as a viscous liquid. After complete addition quenched with 2N hydrochloric acid over 30 min The reaction mixture was extracted with ether dried filtered concentrated