A new synthetic process of bicyclic pyrrolidine intermediate in telaprevir

This paper described a practical process for the preparation of bicyclic pyrrolidine intermediate of telaprevir. The racemate, (3αR, 6αS)-octahydro-cyclopenta［c］pyrrole-1-carboxylic acid hydrochloride( 4 )was synthesized from 3-azabicyclo［3. 3. 0］nonane hydrochloride( 9 ) via chlorination of an imine, basic elimination, sulfonation, cyanation, and acid hydrolysis. The target product, (1S, 3αR, 6αS)-octahydrocyclopenta［c］pyrrole-1-carboxylic-t-butylester oxalate( 1 )was synthesized in an overall yield of about 26. 4% from the free amino acid of compound 4 via Boc protection of the imino, chemical resolution, t-butyl esterification of the carboxyl group, imino deprotection, and formation of the oxalate salt. The convergent synthetic process of compound 1 highlights the ease of operation and high stereoselectivity, and thus should be applicable for large-scale production.