An Efficient Synthesis of a Potent PPARpan Agonist

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• 作者：Jiasheng Guo ; Greg A. Erickson ; Russ N. Fitzgerald ; Richard T. Matsuoka ; Stephen W. Rafferty ; Matthew J. Sharp ; Barry R. Sickles ; James C. Wisowaty
• 刊名：Journal of Organic Chemistry
• 出版年：2006
• 出版时间：October 13, 2006
• 年：2006
• 卷：71
• 期：21
• 页码：8302 - 8305
• 全文大小：84K
• 年卷期：v.71,no.21(October 13, 2006)
• ISSN：1520-6904

文摘

An efficient synthesis of 2-{4-[({4-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)thio]phenoxy}-2-methylpropanoic acid(1), a potent PPARpan agonist, is described. The seven-stepsynthesis, which afforded 1 in 30% overall yield, includes ahighly regioselective carbon-sulfur bond formation viacoupling of a bishydroxymethylthiazole (3) with 4-hydroxythiophenol, displacement of the remaining alcohol througha three-step telescoped sequence involving an efficientcleavage of an aryl mesylate, and an efficient and practicalmethod of introducing an isobutyric acid fragment.