(3S)-3-hydroxy-3-phenylpropanenitrile

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

Procedure: To a 250 round bottom flask were sequentially added 10.0 g of (R)-styrene oxide, 40 ml of 1,2-dichloroethane, 40 ml of 1N potassium hydroxide, 5.96 g of potassium cyanide and 267 mg of tetrabutylammonium bromide. The resulting mixture was heated at reflux for 6 hours. The reaction mixture was cooled and diluted with 1N potassium hydroxide, and extracted with diethyl ether. The ether extracts were combined and washed twice with a saturated sodium chloride solution. The organics layer was dried over magnesium sulfate and concentrated in vacuo. The resulting yellow oil was vacuum distilled at 13 mm pressure and the distillate collected at 140°-180° C. providing 4.11 g of title intermediate. The resulting mixture was heated at reflux for 6 hours The reaction mixture was cooled extracted with diethyl ether washed twice with a saturated sodium chloride solution The organics layer was dried over magnesium sulfate concentrated in vacuo distilled at 13 mm pressure the distillate collected at 140°-180° C.

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

Procedure: A mixture of 40.0 g of (R)-styrene oxide, 31.12 g of acetone cyanohydrin, 36.96 g of triethylamine, and 150 ml of tetrahydrofuran was heated at reflux for 18 hours. The reaction mixture was cooled, concentrated in vacuo, diluted with 200 ml of 2N potassium hydroxide, and extracted with diethyl ether. The ether extracts were combined, dried over magnesium sulfate, and concentrated in vacuo providing 34.3 g of the title intermediate. was heated at reflux for 18 hours The reaction mixture was cooled concentrated in vacuo diluted with 200 ml of 2N potassium hydroxide extracted with diethyl ether dried over magnesium sulfate concentrated in vacuo

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

Procedure: A mixture of 40.0 g of (R)-styrene oxide, 31.12 g of acetone cyanohydrin, 36.96 g of triethylamine, and 150 ml of tetrahydrofuran was heated at reflux for 18 hours. The reaction mixture was cooled, concentrated in vacuo, diluted with 200 ml of 2N potassium hydroxide, and extracted with diethyl ether. The ether extracts were combined, dried over magnesium sulfate, and concentrated in vacuo providing 34.3 g of the title intermediate. was heated at reflux for 18 hours The reaction mixture was cooled concentrated in vacuo diluted with 200 ml of 2N potassium hydroxide extracted with diethyl ether dried over magnesium sulfate concentrated in vacuo

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

Procedure: To 10 ml of a THF solution of 1.47 g (10.0 mmol) of the (S)-3-hydroxy-3-phenylpropanenitrile obtained in Example 1, slowly added was 1.23 ml (13.0 mmol) of borane.dimethylsulfide complex. After removing the dimethylsulfide by reducing the pressure, the reaction mixture was refluxed for 2.5 hours. The reaction was stopped by the addition of a methanol/hydrochloric acid solution, and the methanol was distilled off under vacuum. After neutralizing with a 5N aqueous solution of sodium hydroxide, the solvent was distilled off, a further aqueous solution of sodium hydroxide was added to make the reaction solution basic, and this was then extracted with methylene chloride. This methylene chloride solution was dried with anhydrous sodium sulfate, and the solvent was then distilled off under vacuum to give 1.47 g of (S)-3-amino-1-phenylpropanol. The amino group of (S)-3-amino-1-phenylpropanol was monobenzoylated by reaction with benzoyl chloride, and when it was analyzed using a CHIRALCEL OB column (manufactured by Daicel Chemical Industries, Ltd., eluant; n-hexane:2-propanol=90:10) it was found that the optical purity was 98% ee. After removing the dimethylsulfide the reaction mixture was refluxed for 2.5 hours The reaction was stopped by the addition of a methanol/hydrochloric acid solution the methanol was distilled off under vacuum the solvent was distilled off a further aqueous solution of sodium hydroxide was added this was then extracted with methylene chloride This methylene chloride solution was dried with anhydrous sodium sulfate the solvent was then distilled off under vacuum

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

Procedure: A 50 ml Schlenk flask was charged with 7.26 g (50.0 mmol) of benzoylacetonitrile, 18.1 ml (130 mmol) of triethylamine, 5.8 ml (155 mmol) of formic acid, and 31.8 mg (0.05 mmol, S/C=1000) of RuCl[(S,S)-Tsdpen](p-cymene) under an atmosphere of argon, and stirring was carried out at 30° C. for 24 hours. The solution was poured into water and extracted with ether, the organic layer was washed with saturated brine and then dried with anhydrous sodium sulfate, and the solvent was distilled off under vacuum. The crude product so obtained was distilled under vacuum (0.4 mmHg, 145° C.) to give 6.34 g (yield 86%, 1H-NMR) of (S)-3-hydroxy-3-phenylpropanenitrile. When this was analyzed using a CHIRALCEL OJ column (manufactured by Daicel Chemical Industries, Ltd., eluant; n-hexane:2-propanol=20:1) it was found that the optical purity was 98% ee. extracted with ether the organic layer was washed with saturated brine dried with anhydrous sodium sulfate the solvent was distilled off under vacuum The crude product so obtained was distilled under vacuum (0.4 mmHg, 145° C.)

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

Procedure: To a THF solution of (S)-3-phenyl-3-hydroxypropanenitrile was slowly added THF solution of borane dimethyl sulfide complex at room temperature. Methyl sulfide was then distilled from the reaction vessel and the resulting THF solution refluxed for 2.5 h. After cooling to room temperature methanolic HCl was added to the reaction mixture. Methanol and methyl borate were removed by distillation and the reaction mixture neutralized with sodium hydroxide (5N). Extraction of the mixture with dichloromethane,followed by concentration provided the crystalline (S)-3-phenyl-3-hydroxypropylamine. at room temperature Methyl sulfide was then distilled from the reaction vessel the resulting THF solution refluxed for 2.5 h was added to the reaction mixture Methanol and methyl borate were removed by distillation Extraction of the mixture with dichloromethane,followed by concentration

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixed solvent (volume ratio=1:1, 5 mL) of water and methanol and the iridium aqua complex shown in the following Table 1 (0.5 mol % relative to 2-cyanoacetophenone) were mixed, and 2-cyanoacetophenone (1 mmol) and the hydrogen-donor compound shown in the following Table 1 (5 mmol) were added to the obtained solution at room temperature. The obtained mixture was stirred at 70° C. After confirming the disappearance of 2-cyanoacetophenone by thin layer chromatography, the reaction was quenched with brine (20 mL). The reaction mixture was subjected to extraction treatment (three times) with ethyl acetate (20 mL), and the obtained organic layers were combined. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol=20:1) to give (S)-3-phenyl-3-hydroxypropionitrile. The conversion and optical purity are shown in Table 1. were mixed were added to the obtained solution at room temperature the reaction was quenched with brine (20 mL) The reaction mixture was subjected to extraction treatment (three times) with ethyl acetate (20 mL) The combined organic layer was dried over anhydrous sodium sulfate concentrated The obtained residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol=20:1)

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

Procedure: To a 250 round bottom flask were sequentially added 10.0 g of (R)-styrene oxide, 40 ml of 1,2-dichloroethane, 40 ml of 1N potassium hydroxide, 5.96 g of potassium cyanide and 267 mg of tetrabutylammonium bromide. The resulting mixture was heated at reflux for 6 hours. The reaction mixture was cooled and diluted with 1N potassium hydroxide, and extracted with diethyl ether. The ether extracts were combined and washed twice with a saturated sodium chloride solution. The organics layer was dried over magnesium sulfate and concentrated in vacuo. The resulting yellow oil was vacuum distilled at 13 mm pressure and the distillate collected at 140°-180° C. providing 4.11 g of title intermediate. The resulting mixture was heated at reflux for 6 hours The reaction mixture was cooled extracted with diethyl ether washed twice with a saturated sodium chloride solution The organics layer was dried over magnesium sulfate concentrated in vacuo distilled at 13 mm pressure the distillate collected at 140°-180° C.

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

Procedure: A mixture of 40.0 g of (R)-styrene oxide, 31.12 g of acetone cyanohydrin, 36.96 g of triethylamine, and 150 ml of tetrahydrofuran was heated at reflux for 18 hours. The reaction mixture was cooled, concentrated in vacuo, diluted with 200 ml of 2N potassium hydroxide, and extracted with diethyl ether. The ether extracts were combined, dried over magnesium sulfate, and concentrated in vacuo providing 34.3 g of the title intermediate. was heated at reflux for 18 hours The reaction mixture was cooled concentrated in vacuo diluted with 200 ml of 2N potassium hydroxide extracted with diethyl ether dried over magnesium sulfate concentrated in vacuo