4-Methylmorpholine → Methyl (S)-3-(Boc-amino)-4-hydroxybutanoate

Participants

Reaction Steps

To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-4-methoxy-4-oxobutanoic acid (9.0 g, 35.7 mmol) in THF (180 mL) at −10° C. was added N-methylmorpholine (3.9 mL, 35.7 mmol) followed by ethyl chloroformate (3.91 g, 35.7 mmol). After 10 min, the mixture was transferred slowly to a mixture of NaBH4 (2.7 g, 71.4 mmol) and ice water (900 mL). The resulting solution was stirred for 1 h, NaHCO3 (˜20 g) was added, and the organic layer was separated. The aqueous layer was extracted with EtOAc (4×200 mL). The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL), dried over Na2SO4, and concentrated to give (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.06 g, 85%) as an oil. MS m/z 234 (M+H+).

Provenance & Evidence