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

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• 作者：Shira D. Halperin ; Daniel Kwon ; Michael Holmes ; Erik L. Regalado ; Louis-Charles Campeau ; Daniel A. DiRocco ; Robert Britton
• 刊名：Organic Letters
• 出版年：2015
• 出版时间：November 6, 2015
• 年：2015
• 卷：17
• 期：21
• 页码：5200-5203
• 全文大小：354K
• ISSN：1523-7052

文摘

Late-stage C鈥揌 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 纬-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鈥揌 fluorination reaction compares favorably with several generations of classical 纬-fluoroleucine process syntheses.