Pyridine → Methyl (S)-(-)-2-Isocyanato-3-methylbutyrate

Participants

Reaction Steps

A mixture of L-valine methyl ester hydrochloride (10.0 g, 59.9 mmol), DCM (300 mL), and pyridine (19.3 mL, 240 mmol) was cooled in an ice/salt bath and a solution of 20% phosgene in PhMe (35.6 mL, 719 mmol) added dropwise, maintaining the reaction temperature below 5° C. during the addition. A white suspension resulted and after 1.5 hours, the reaction mixture was poured into ice-cold 1M HCl and extracted with DCM (2×500 mL). The combined organic phases were washed with brine, dried over anhydrous MgSO4, and evaporated. Flash column chromatography on silica (95 hexanes/5 EtOAc) gave the title compound as a colorless oil (6.43 g). 1H NMR (CDCl3 500 MHz) δ 3.94 (d, J=4.0 Hz, 1H), 3.82 (s, 3H), 2.24 (m, 1H), 1.03 (3, J=7.0 Hz, 3H), 0.90 (d, J=6.5 Hz, 3H) ppm.

Provenance & Evidence