Preparation of 5-(2-Methoxy-4-nitrophenyl)oxazole: A Key Intermediate for the Construction of VX-497

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• 作者：R. Jason Herr ; David J. Fairfax ; Harold Meckler ; and Jeffrey D. Wilson
• 刊名：Organic Process Research & Development
• 出版年：2002
• 出版时间：September 2002
• 年：2002
• 卷：6
• 期：5
• 页码：677 - 681
• 全文大小：66K
• 年卷期：v.6,no.5(September 2002)
• ISSN：1520-586X

文摘

A process for the multigram preparation of 5-(2-methoxy-4-nitrophenyl)oxazole, a key intermediate for the preparation ofthe hepatitis C drug candidate VX-497 (merimepodib), has beenachieved in good yield from a commercially available dye. Earlystudies focused on the preparation of the requisite aldehydeby the Beech reaction. A second approach utilized a palladium(0)-catalyzed formylation of an aryl diazonium species, whichwas followed by condensation of the aldehyde with tosylmethylisocyanide (TosMIC) to provide the required oxazole. This two-step method has been carried out to provide multigram samplesof this key intermediate in 75% overall yield and >95% purityfrom the commercially available Fast Red B tetrafluoroboratesalt.