Benzaldehyde → (2S)-2-(benzylamino)-3-hydroxypropanoic acid

Participants

Reaction Conditions

Reaction Steps

To a reaction vessel was added solid serine methyl ester hydrochloride (1 eq). Methanol (2.85 vol) was added and agitation was started. Triethylamine (1 eq) was added over 10 min while maintaining the temperature at 14˜18° C. Stirring was continued until all solids dissolved. The mixture was cooled to 10° C. and benzaldehyde (1 eq) was added over 15 min while maintaining the temperature between 11˜15° C. The reaction was held for 30 min at 8˜12° C. Solid sodium borohydride (4 eq) was added over 2 hr while maintaining the temperature at 10˜20° C. The reaction was held for 30 min at 14˜16° C. In a separate flask, methanol (1.15 vol) and water (1.72 vol) were added. Sodium hydroxide, 50 wt/wt % in water (3 eq) was added and the resulting solution was cooled to 15° C. The Schiff's base was transferred to this mixture over 1 hr maintaining the internal temperature between 16˜22° C. Water was added (1.72 vol), followed by concentrated HCl, 12.2 M in water (2.67 eq) while maintaining the temperature at 15˜25° C. to adjust the pH to 9.5. The mixture was filtered and the filter-cake was washed with two portions of water (0.58 vol). The combined aqueous portions were washed two times with ethyl acetate (5.75 vol). The mixture was cooled from 25° C. to 15° C., and concentrated HCl was added, 12.2 M in water (0.89 eq), until the pH of the mixture reached 6.5, while maintaining the temperature between 17–22° C. The mixture was held for 15˜25 hr at 5° C. and then the solids were collected on a filter funnel. The filter-cake was washed with two portions of water (1.43 vol) and two portions of heptane (1.43 vol). The wet solid was transferred to a drying tray, and dried at 45° C. for 21 h to afford the product.

Provenance & Evidence