An Efficient Synthesis of a Multipotent Eicosanoid Pathway Modulator†

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• 作者：Matthew H. Yates* ; Thomas M. Koenig ; Neil J. Kallman ; Christopher P. Ley ; David Mitchell
• 刊名：Organic Process Research & Development
• 出版年：2009
• 出版时间：March 20, 2009
• 年：2009
• 卷：13
• 期：2
• 页码：268-275
• 全文大小：285K
• 年卷期：v.13,no.2(March 20, 2009)
• ISSN：1520-586X

文摘

An efficient, scalable synthesis of the multipotent eicosanoid pathway modulator 2-[3-[3[[5-ethyl-4′-fluoro-2-hydroxyl[1,1′-biphenyl]-4-yl]oxy]-propoxy]2-propoxylphenoxy]benzoic acid (1) is described. The process consists of nine chemical steps with the longest linear sequence having six isolations. Palladium metal-mediated cross-coupling assembles the biaryl fragment, and selective S_NAr chemistry is used to construct the resorcinol fragment. The synthesis converges at a phenolic coupling with an alkyl chloride to give the core structure of the active pharmaceutical ingredient (API). Further elaborations of the core and salt formation provides the final API. This process produced the drug candidate in 41% overall yield at multikilogram scale.