Methyl chloroformate → N-(methoxycarbonyl)-L-valyl-L-proline tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of sodium carbonate (110.5 g) in water (1.5 liters) and L-Valyl-L-Proline tert-butyl ester in tetrahydrofuran (THF; 1 liter) were combined and cooled to 0° C. The mixture was diluted with ether (400 ml) and methyl chloroformate (39.4 g) was added dropwise. The reaction mixture was then allowed to warm ambient temperature over 2 hours. The layers were separated and the organic phase was washed twice with 1M hydrochloric acid, followed by saturated aqueous sodium bicarbonate solution and brine. The aqueous phase was extracted with ether. All organic phases were combined and dried (MgSO4) and the solvent removed to give N-(methoxycarbonyl)-L-valyl-L-proline tert-butyl ester (125.9 g); 1H NMR (300 MHz, DMSO/d4-trifluoroacetic acid): 4.23 (dd, 1H), 4.06 (d, 1H), 3.78 (m, 1H), 3.57 (m, 1H), 3.55 (s, 3H), 2.16 (m, 1H), 1.95 (m, 3H), 1.80 (m, 1H), 1.42 (s, 9H), 0.94 (m, 6H); MS: m/z=329 (M+1).

Provenance & Evidence