Practical synthesis of methyl 7-(3-hydroxy-5-oxocyclopent-1-en-1-yl)-heptanoate

Abstract

The key intermediate of misoprostol, methyl 7-(3-hydroxy-5-oxocyclopent-1-en-1-yl)-heptanoate was prepared from commercially available suberic acid in 40% yield over five steps. The key step involved a ZnCl2 catalyzed Friedel-Crafts reaction between furan and 2,9-oxonanedione. Sulfuric acid catalyzed methylation of 8-(furan-2-yl)-8-oxooctanoic acid followed by sequential reduction and ZnCl2 catalyzed Piancatelli rearrangement resulted in the formation of the key intermediate of misoprostol.

Keywords

• Misoprostol
• Dehydrate cyclization
• Friedel-Crafts acylation
• Piancatelli rearrangement