Benzaldehyde → (R)-2-(Benzylamino)-3-hydroxypropanoic acid

Participants

Reaction Conditions

Reaction Steps

As per the procedures of WO2005058245, a mixture of D-serine methyl ester hydrochloride (98.84 g, 635.3 mmol) in MeOH (280 mL) was cooled to 10° C. To the mixture was slowly added triethylamine (88.5 mL, 635.0 mmol). The mixture was warmed to room temperature and the resulting solution was cooled to 10° C. To the solution was added benzaldehyde (64 mL, 630.2 mmol), and the solution was stirred for 30 min. To the solution was added sodium borohydride (24.03 g, 635.2 mmol) portionwise over 30 min, and the mixture was stirred for a further 30 min. In a separate flask, MeOH (114 mL) was added to water (170 mL), and to this solution was added a solution of NaOH (77.25 g, 1931 mmol) in water (155 mL). The solution was cooled to 15° C., and the reductive amination mixture was slowly added to the NaOH-water-MeOH solution over 15 min. The solution was stirred and warmed to room temperature over 30 min, and water (170 mL) was added, followed by sufficient 6 N aqueous HCl to adjust the pH to 9.5. The solution was washed with EtOAc (2×60 mL), and sufficient 6 N aqueous HCl was added to adjust the pH to 6.5. The mixture was cooled to 0° C. and held overnight. The resulting solid was collected by vacuum filtration and washed with water (2×200 mL) followed by heptane (2×200 mL). The white solid was dried at 40° C. under high vacuum for 3 days to afford N-(phenylmethyl)-D-serine (79.51 g, 64%). LCMS: (M+H)+: 196.1.

Provenance & Evidence