Process for the synthesis of N-((S)-1-(ethoxycarbonyl)butyl)-(S)-alanine and use in the synthesis of perindopril

摘要

Producing N-((S)-1-ethoxycarbonyl-butyl)-(S)-alanine (I). Production of N-((S)-1-ethoxycarbonyl-butyl)-(S)-alanine of formula (I), comprising: (1) reacting ethyl glyoxylate (III) with allyl-zinc bromide (IV) to give ethyl 2-hydroxy-4-pentenoate (V); (2) optically resolving (V) by enzymatic hydrolysis to give ethyl (2R)-2-hydroxy-4-pentenoate of formula (Va); (3) converting (Va) into the triflate of formula (VI); (4) reacting (VI) with an (S)-alanine ester of formula (VII) to give an ethyl 2-(substituted amino)-4-pentenoate of formula (VIII); and (5) subjecting (VIII) to catalytic hydrogenation and deprotection of the acid function to give (I). R = 1-6C alkyl or benzyl. An Independent claim is included for the intermediate (VI) as a new compound.