The Synthesis of Two Potent β-3 Adrenergic Receptor Agonists

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• 作者：Paul A. Bradley ; Robert J. Carroll ; Yann C. Lecouturier ; Robert Moore ; Pierre Noeureuil ; Bhairavi Patel ; Jonathan Snow ; Simon Wheeler
• 刊名：Organic Process Research & Development
• 出版年：2010
• 出版时间：November 19, 2010
• 年：2010
• 卷：14
• 期：6
• 页码：1326-1336
• 全文大小：245K
• 年卷期：v.14,no.6(November 19, 2010)
• ISSN：1520-586X

文摘

This contribution describes the initial preparation of two potent β-3 receptor agonists 1 and 2. Subsequent scale up of these two compounds was required for further evaluation and proceeded via a common key amine intermediate 24. Synthesis of this key intermediate by way of a Ritter reaction was a vital step in the sequence. Enantioselective Noyori hydrogenation reactions gave access to the chiral epoxides necessary to make the target compounds. Chemistry was developed for the selective dehalogenation of the 2-chloropyridyl group in the presence of a sensitive isoxazole unit to provide access to 1.