PRODUCTION OF ALKOXYCARBONYL DIPEPTIDE INTERMEDIATE IN SYNTHESIZING LISINOPRIL

摘要

PROBLEM TO BE SOLVED: To obtain in high yield the subject compound useful as e.g. a raw material for antihypertensives by protecting both amino groups of L-lysine in its alkaline aqueous solution followed by reaction with thionyl chloride and L-proline successively in the presence of DMF. SOLUTION: This compound, an alkoxycarbonyl dipeptide of formula IV, useful as e.g. an intermediate for synthesizing lisinopril as an antihypertensive, is obtained at low cost in high yield by the following procedure: L-lysine in its alkaline aqueous solution is treated with an alkyl chloroformate of formula I [R is a (substituted) 1-6C alkyl] to protect both amino functional groups of the L-lysine to form a product of formula II, which, in turn, is reacted with thionyl chloride in an inert solvent in the presence of N,N-dimethylformamide to form the N-carboxyanhydride of an N6-(alkoxycarbonyl)-L-lysine of formula III, which, in turn, is reacted with L-proline in a hydrous acetone alkaline medium.