An Efficient and Scalable Synthesis of tert-Butyl (3aR,6aS)-5-Oxohexahydrocyclo penta[c]pyrrole-2(1H)-carboxylate: A Pharmacologically Important Intermediate

Abstract

Hexahydrocyclopentapyrrolone derivatives constitute an important class of bicycles, and it represents an essential pharmacophore for diversified pharmacological activities. A highly efficient process for the synthesis of tert-butyl(3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate 1 has been developed. The improved process involves transformation of isoindole 4 to diacid 5, using an inexpensive KMnO 4 mediated oxidative cleavage as a key step. The developed process was cost-effective, high yielding, kilogram scalable, and commercially viable for synthesis of 1.