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

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).

1. waitleft
2. customThe layers were separated
3. washthe organic layer was then washed with saturated sodium bicarbonate solution
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under vacuum
6. customto afford 7.05 g of the crude product
7. temperaturecooled to 0° C
8. stirringAfter stirring for 30 min
9. stirringand the reaction mixture was stirred for another 5 min
10. customthe layers were separated
11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
12. concentrationconcentrated under vacuum

ORD record

ord-95cfd0ad0d8548fba061fe9dd98e1f77

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07288541B2