Synthesis of (±)-Entecavir

Abstract

A practical synthesis of (±)-entecavir has been developed on the basis of Corey (±)-lactone diol. The key stage is the synthesis of (1R*,3R*,4S*)-4-(1-ethoxyethoxy)-3-[(1-ethoxyethoxy)methyl]-2-methylidene­cyclo­pentan-1-ol by oxidative decarboxylation of 2-{(1S*,2R*,3S*,5R*)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-(1-ethoxyethoxy)-2-[(1-ethoxyethoxy)methyl]cyclopentyl}acetic acid with lead tetraacetate.