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

Participants

Reaction Steps

D-Serine methyl ester hydrochloride (10.0 g, 64.3 mmol) in MeOH (29 mL) was cooled in ice water bath. TEA (9.00 mL, 64.6 mmol) was added dropwise via syringe and reaction was warmed to rt. When the solution was homogenous, it was re-cooled with an ice water bath. Benzaldehyde (6.46 mL, 63.6 mmol) was added dropwise via syringe and the reaction was stirred for 30 min. NaBH4 (7.84 g, 64.3 mmol) was then added in portions over 40 min and the resultant mixture was stirred for 1 h. To a separate flask, cooled in an ice bath, containing MeOH (12 mL) and H2O (17 mL) was added NaOH (7.84 g, 195 mmol) in H2O (16 mL). To this solution was added the NaBH4 solution followed by H2O (17 mL). The reaction was warmed to rt and the pH was adjusted to 9.5 using 6N HCl. The reaction mixture was washed twice with EtOAc and the pH was adjusted to 6.5 with 6N HCl. The resultant suspension was cooled in a refrigerator for 1 h. The solid was filtered, washed twice with H2O (20 mL), twice with heptane (20 mL) and dried overnight at 45° C. in a vacuum oven to give the title compound of step A (4.91 g, 25.2 mmol, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.08-3.17 (m, 1H), 3.57-3.68 (m, 2H), 3.94 (q, J=13.2 Hz, 2H), 7.26-7.35 (m, 4H), 7.37-7.40 (m, 3H), 7.44-8.45 (br.s., 1H). [α]D20° C.=−5.3, I=100 mm, c=1.0 in 6N HCl.

Provenance & Evidence