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

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 27.8 g (120.0 mmol) of N-Boc-L-Norleucine in 150 mL of dichloromethane at −40° C. was added a solution of 18.4 mL (151.5 mmol) of 1-methylpiperidine in 40 mL of dichloromethane over 20 min. Then, 13.9 mL (145.4 mmol) of ethyl chloroformate in 40 mL of dichloromethane was added over 30 min and the reaction mixture was stirred at −40° C. for 2.5 h. A solution of 14.2 g (145.4 mmol) of N,O-dimethylhydroxylamine hydrochloride and 18.4 mL (151.5 mmol) of 1-methylpiperidine in 90 mL of dichloromethane was added over 45 min, then the reaction mixture was allowed to slowly warm to room temperature and was stirred for 18 h. It was then washed with 100 mL of water, 100 mL of 1% hydrochloric acid (2×), 100 mL of saturated aqueous sodium bicarbonate, and dried over anhydrous magnesium sulfate. Concentration in vacuo afforded 35.0 g (quantitative yield) of crude tert-butyl (1S)-1-{[methoxy(methyl)amino]carbonyl}pentylcarbamate 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