New Synthesis of 2,2‐Bis(hydroxymethyl) methylenecyclopropane, a Key Intermediate for Antiviral Cyclopropavir

Abstract

Synthesis of 2,2‐bis(hydroxymethyl)methylenecyclopropane (2) is described. Cyclopropane dicarboxylate 3 was reduced to diol 4, which was acetylated to give diacetate 5. Acetoxy‐bromo elimination afforded methylenecyclopropane 6. Debenzylation gave the title compound 2.

Keywords:

• acetoxy‐bromo elimination
• antivirals
• cyclopropanes
• cyclopropavir
• methylenecyclopropanes

Acknowledgments

We thank L. M. Hryhorczuk from the Central Instrumentation Facility, Department of Chemistry, Wayne State University, for mass spectra. The work described herein was supported by SBIR Grant 5 R44 AI0554135 to Microbiotix, Inc., Worcester, Massachusetts, and Research Grant 1 RO1 CA32779 from the National Institutes of Health, Bethesda, Maryland, USA.