Methyl chloroformate → N-(Methoxycarbonyl)-L-tert-leucine

Participants

Reaction Conditions

Reaction Steps

A solution of L-tert-Leucine (25 g, 190.58 mmol) in a mixture of dioxane (100 mL) and aqueous NaOH solution (315 mL, 2N) was treated dropwise with methyl chloroformate (29.3 mL, 379.19 mmol), keeping the internal temperature below 50° C. The mixture was warmed to 60° C. and stirred for 18 hours, cooled to 25° C. and extracted with dichloromethane. The aqueous phase was cooled to 0° C. and the pH was adjusted to about 1-2 with concentrated HCl. The mixture was partitioned between ethyl acetate and water. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. A solution of the concentrate in ether was treated with hexanes to afford the crystalline product (33.22 g, 92% yield), which was collected by filtration.

Provenance & Evidence