ethyl (2S)-2-phenylmethoxypropanoate

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

Procedure: A solution of 1.0M DIBAL (diisobutylaluminum hydride) in hexane (10 ml) was added dropwise to a stirred solution of ethyl (S)-2-(benzyloxy)propionate (obtained in Preparation 7) (2.08 g) in methylene chloride (20 ml) at −78° C. (dry-ice/acetone) for 5 minutes under nitrogen atmosphere. After 20 minutes, methanol (1.6 ml) was added dropwise to the mixture at −78° C., and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was filtered through a pad of Celite, and the solid on the filter was washed with methylene chloride. The combined filtrates were concentrated in vacuo. The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1) to give (S)-2-(benzyloxy)propionaldehyde (810 mg). The mixture was filtered through a pad of Celite the solid on the filter was washed with methylene chloride The combined filtrates were concentrated in vacuo The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: A solution of 1.0M DIBAL (diisobutylaluminum hydride) in hexane (10 ml) was added dropwise to a stirred solution of ethyl (S)-2-(benzyloxy)propionate (obtained in Preparation 7) (2.08 g) in methylene chloride (20 ml) at −78° C. (dry-ice/acetone) for 5 minutes under nitrogen atmosphere. After 20 minutes, methanol (1.6 ml) was added dropwise to the mixture at −78° C., and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was filtered through a pad of Celite, and the solid on the filter was washed with methylene chloride. The combined filtrates were concentrated in vacuo. The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1) to give (S)-2-(benzyloxy)propionaldehyde (810 mg). The mixture was filtered through a pad of Celite the solid on the filter was washed with methylene chloride The combined filtrates were concentrated in vacuo The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: Trifluoromethanesulfonic acid (1.13 g) was added to a stirred mixture of ethyl (S)-(−)-lactate (5.90 g) and benzyl 2,2,2-trichloroacetimidate (15.15 g) in cyclohexane (70 ml) and methylene chloride (35 ml) at room temperature under nitrogen atmosphere. After being stirred for 18 hours, the reaction mixture was filtered. The filtrate was diluted with cyclohexane, and then washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1) to give ethyl (S)-2-(benzyloxy)propionate (6.48 g). the reaction mixture was filtered The filtrate was diluted with cyclohexane washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml) The organic layer was dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: Trifluoromethanesulfonic acid (1.13 g) was added to a stirred mixture of ethyl (S)-(−)-lactate (5.90 g) and benzyl 2,2,2-trichloroacetimidate (15.15 g) in cyclohexane (70 ml) and methylene chloride (35 ml) at room temperature under nitrogen atmosphere. After being stirred for 18 hours, the reaction mixture was filtered. The filtrate was diluted with cyclohexane, and then washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1) to give ethyl (S)-2-(benzyloxy)propionate (6.48 g). the reaction mixture was filtered The filtrate was diluted with cyclohexane washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml) The organic layer was dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: A solution of 1.0M DIBAL (diisobutylaluminum hydride) in hexane (10 ml) was added dropwise to a stirred solution of ethyl (S)-2-(benzyloxy)propionate (obtained in Preparation 7) (2.08 g) in methylene chloride (20 ml) at −78° C. (dry-ice/acetone) for 5 minutes under nitrogen atmosphere. After 20 minutes, methanol (1.6 ml) was added dropwise to the mixture at −78° C., and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was filtered through a pad of Celite, and the solid on the filter was washed with methylene chloride. The combined filtrates were concentrated in vacuo. The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1) to give (S)-2-(benzyloxy)propionaldehyde (810 mg). The mixture was filtered through a pad of Celite the solid on the filter was washed with methylene chloride The combined filtrates were concentrated in vacuo The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: Trifluoromethanesulfonic acid (1.13 g) was added to a stirred mixture of ethyl (S)-(−)-lactate (5.90 g) and benzyl 2,2,2-trichloroacetimidate (15.15 g) in cyclohexane (70 ml) and methylene chloride (35 ml) at room temperature under nitrogen atmosphere. After being stirred for 18 hours, the reaction mixture was filtered. The filtrate was diluted with cyclohexane, and then washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1) to give ethyl (S)-2-(benzyloxy)propionate (6.48 g). the reaction mixture was filtered The filtrate was diluted with cyclohexane washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml) The organic layer was dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: The water layer at the time of the extraction with ethyl acetate in Example 3 was collected in its entirety, and was then adjusted to pH 2 with 10% hydrochloric acid. The water layer was then extracted twice with ethyl acetate (100 mL). After the organic layers were combined and dried, the solvent was distilled off to obtain (S)-benzyloxypropionic acid [0.83 g (48.0%), 96% ee]. An aliquot (0.8 g, 4.4 mmol) of the (S)-benzyloxypropionic acid was dissolved in ethanol (10 mL), followed by the addition of concentrated sulfuric acid (0.01 mL). The thus-prepared mixture was then heated under reflux. Eight hours later, the solvent was distilled off, and the residue was extracted with ethyl acetate (20 mL). The extract was washed with a 5% aqueous solution of sodium hydrogencarbonate (10 mL) and water (10 mL), the organic layer was dried, and the solvent was distilled off to obtain (S)-ethyl benzyloxypropionate. It was dissolved in toluene (10 mL), and under ice-cooled stirring, sodium ethoxide (0.33 g, 1.1 eq) was added, followed by stirring at room temperature for 14 hours. By gas chromatography making use of an optically active column, completion of the racemization was confirmed. Thereafter, the reaction mixture was added dropwise into a 10% aqueous solution of citric acid (10 mL). After the organic layer was washed with water (10 mL) and then dried, the solvent was distilled off to afford the title compound (0.74 g). 1H-NMR spectrum data of the compound were in conformity with those of the compound in Example 1. This racemate can be used as a feed for such asymmetric ester hydrolysis as in Examples 1 to 4. The thus-prepared mixture was then heated under reflux Eight hours later, the solvent was distilled off the residue was extracted with ethyl acetate (20 mL) The extract was washed with a 5% aqueous solution of sodium hydrogencarbonate (10 mL) and water (10 mL) the organic layer was dried the solvent was distilled off

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

Procedure: A solution of 1.0M DIBAL (diisobutylaluminum hydride) in hexane (10 ml) was added dropwise to a stirred solution of ethyl (S)-2-(benzyloxy)propionate (obtained in Preparation 7) (2.08 g) in methylene chloride (20 ml) at −78° C. (dry-ice/acetone) for 5 minutes under nitrogen atmosphere. After 20 minutes, methanol (1.6 ml) was added dropwise to the mixture at −78° C., and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was filtered through a pad of Celite, and the solid on the filter was washed with methylene chloride. The combined filtrates were concentrated in vacuo. The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1) to give (S)-2-(benzyloxy)propionaldehyde (810 mg). The mixture was filtered through a pad of Celite the solid on the filter was washed with methylene chloride The combined filtrates were concentrated in vacuo The obtained residue was purified by silica gel (35 g) chromatography eluted with hexane/ethyl acetate (30:1)

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

Procedure: Trifluoromethanesulfonic acid (1.13 g) was added to a stirred mixture of ethyl (S)-(−)-lactate (5.90 g) and benzyl 2,2,2-trichloroacetimidate (15.15 g) in cyclohexane (70 ml) and methylene chloride (35 ml) at room temperature under nitrogen atmosphere. After being stirred for 18 hours, the reaction mixture was filtered. The filtrate was diluted with cyclohexane, and then washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1) to give ethyl (S)-2-(benzyloxy)propionate (6.48 g). the reaction mixture was filtered The filtrate was diluted with cyclohexane washed successively with saturated NaHCO3 solution (100 ml)and H2O (100 ml) The organic layer was dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel (260 g) chromatography eluted with hexane/ethyl acetate (30:1)