Citric Acid → tert-butyl N-((2S)-1-oxopropan-2-yl)carbamate

Participants

Reaction Steps

To a solution of 10.7 g (57.0 mmol) of (2S)-2-[(tert-butoxycarbonyl)amino]propanoic acid in 200 mL of dichloromethane at 0° C. was added 12.0 g (74.1 mmol) of carbonyldiimidazole, 10.39 mL (74.1 mmol) of triethylamine, and 7.08 g (74.1 mmol) of N,O-dimethylhydroxylamine hydrochloride. The reaction mixture was warmed to room temperature and left stirring for 16 h. Diethyl ether was then added, followed by the addition of 10% hydrochloric acid. The layers were separated, and the organic layer was then washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate and concentrated under vacuum to afford 7.05 g of the crude product. Then, 7.05 g (30.4 mmol) of the crude tert-butyl (1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethylcarbamate was dissolved in 109 mL of tetrahydrofuran and cooled to 0° C. A 1.0 M solution of 45.6 mL (45.6 mmol) of lithium aluminum hydride in tetrahydrofuran was then added gradually over 20 min. After stirring for 30 min, 10% citric acid solution was added. and the reaction mixture was stirred for another 5 min. The reaction mixture was diluted with diethyl ether and the layers were separated. The organic layer was dried over anhydrous magnesium sulfate and concentrated under vacuum to afford 5.25 g (>99%) of tert-butyl (1S)-1-methyl-2-oxoethylcarbamate, which was carried into the next step directly. 1H-NMR (300 MHz, CDCl3) δ 9.58 (s, 1H), 5.15 (m, 1H), 4.25 (m, 1H), 1.35 (s, 9H), 1.27 (d, J=7 Hz, 3H).

Provenance & Evidence