An Approach to the Synthesis of a Hepatitis C Virus Inhibitor through a Proline-Catalyzed 1,3-Dipolar Cycloaddition Using Acrolein

Abstract

An efficient and easy protocol for performing 1,3-dipolar cycloaddition using azomethine ylides and acrolein is presented. The reaction catalyzed by d-proline allows the synthesis of C-3 unsubstituted pyrrolidines. The application of this methodology to the synthesis of an advanced intermediate in the preparation of a Hepatitis C virus inhibitor is presented. Final attempts to complete the synthesis of the target inhibitor results in the preparation of its C-4 epimer in good overall yield