Synthesis of 5-amino- and 5-hydroxy-3,3-difluoropiperidines?

Organic & Biomolecular Chemistry Pub Date: 2010-07-29 DOI: 10.1039/C0OB00231C

Abstract

Synthetic routes toward new 5-amino- and 5-hydroxy-3,3-difluoropiperidines, which are of high interest as building blocks in medicinal chemistry, are described. The key step involves the N-halosuccinimide-induced cyclization of 2,2-difluoro-4-pentenylamines toward 5-halo-3,3-difluoropiperidines, which were used to synthesize 5-amino-3,3-difluoropiperidine. In a second strategy, iodolactonization of 2,2-difluoro-4-pentenoic acid gave the corresponding γ-lactone, which was transformed into 5-hydroxy-3,3-difluoropiperidine.

Graphical abstract: Synthesis of 5-amino- and 5-hydroxy-3,3-difluoropiperidines
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