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

Temperature

-40 °C

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).

1. temperatureto slowly warm to room temperature
2. stirringwas stirred for 18 h
3. washIt was then washed with 100 mL of water, 100 mL of 1% hydrochloric acid (2×), 100 mL of saturated aqueous sodium bicarbonate
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationConcentration in vacuo

ORD record

ord-1c4c3ea5f21e4e3095d45e079b7f19a7

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07288541B2