Ethyl chloroformate → tert-butyl (1S)-1-{[methoxy(methyl)amino]carbonyl}pentylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (2S)-2-[(tert-butoxycarbonyl)amino]hexanoic acid (27.8 g, 120.0 mmol) in dichloromethane (150 mL) at −40° C. was added a solution of 1-methylpiperidine (18.4 mL, 151.5 mmol) in dichloromethane (40 mL) over 20 min. Ethyl chloroformate (13.9 mL, 145.4 mmol) in dichloromethane (40 mL) was then added over 30 min and the reaction mixture was stirred at −40° C. for 2.5 h. A solution of N,O-dimethylhydroxylamine hydrochloride (14.2 g, 145.4 mmol) and 1-methylpiperidine (18.4 mL, 151.5 mmol) in dichloromethane (90 mL) was added over 45 min, and the reaction mixture was allowed to slowly warm to ambient temperature. It was stirred for 18 h, and then washed with water (100 mL), 1% hydrochloric acid (2×100 mL), and saturated aqueous sodium bicarbonate (100 mL). The organic layer was then dried with magnesium sulfate and concentrated in vacuo to afford the desired title compound (35.0 g, 106%) as a thick oil. 1H NMR (400 MHz, DMSO-d6): δ 6.94 (d, J=8 Hz, 1H), 4.35-4.25 (m, 1H), 3.68 (s, 3H), 3.05 (s, 3H), 1.52-1.36 (m, 2H), 1.32 (s, 9H), 1.30-1.14 (m, 4H), 0.80 (t, J=6 Hz, 3H).

Provenance & Evidence