Remote Electronic Control in the Regioselective Reduction of Succinimides: A Practical, Scalable Synthesis of EP4 Antagonist MF-310

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• 作者：Carmela Molinaro ; Danny Gauvreau ; Gregory Hughes ; Stephen Lau ; Sophie Lauzon ; Rmy Angelaud ; Paul D. O’ ; Shea ; Jacob Janey ; Michael Palucki ; Scott R. Hoerrner ; Conrad E. Raab ; Rick R. Sidler ; Miche
• 刊名：Journal of Organic Chemistry
• 出版年：2009
• 出版时间：September 4, 2009
• 年：2009
• 卷：74
• 期：17
• 页码：6863-6866
• 全文大小：773K
• 年卷期：v.74,no.17(September 4, 2009)
• ISSN：1520-6904

文摘

A practical large-scale chromatography-free synthesis of EP4 antagonist MF-310, a potential new treatment for chronic inflammation, is presented. The synthetic route provided MF-310 as its sodium salt in 10 steps and 17% overall yield from commercially available pyridine dicarboxylate 7. The key features of this sequence include a unique regioselective reduction of succinimide 2 controlled by the electronic properties of a remote pyridine ring, preparation of cyclopropane carboxylic acid 3 via a Corey−Chaykovsky cyclopropanation, and a short synthesis of sulfonamide 5.