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Development of a Direct Photocatalytic C–H Fluorination for the Preparative Synthesis of Odanacatib

By Halperin, Shira D.; Kwon, Daniel; Holmes, Michael; Regalado, Erik L.; Campeau, Louis-Charles; DiRocco, Daniel A.; Britton, Robert

Published on CMKC

Abstract

Late-stage C–H fluorination is an appealing reaction for medicinal chemistry. However, the application of this strategy to process research appears less attractive due to the formation and necessary purification of mixtures of organofluorines. Here we demonstrate that γ-fluoroleucine methyl ester, an intermediate critical to the large-scale synthesis of odanacatib, can be accessed directly from leucine methyl ester using a combination of the decatungstate photocatalyst and N-fluorobenzenesulfonimide in flow. This efficient C–H fluorination reaction compares favorably with several generations of classical γ-fluoroleucine process syntheses.

Journal

Organic Letters. Volume 17, 2015, 5200-5203

DOI

10.1021/acs.orglett.5b02532

Type of publication

Peer-reviewed journal

Affiliations

  • Simon Fraser University
  • Merck Research Laboratories

Article Classification

Research Article

Classification Areas

  • Intermediate

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