Selection and Scale-Up Evaluation of an Alternative Route to (鈭?-(3R,4R)-1-Benzyl-4-(benzylamino)piperidin-3-ol

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• 作者：Ian S. Young ; Adrian Ortiz ; James R. Sawyer ; David A. Conlon ; Frederic G. Buono ; Simon W. Leung ; Justin L. Burt ; Eric W. Sortore
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：September 21, 2012
• 年：2012
• 卷：16
• 期：9
• 页码：1558-1565
• 全文大小：555K
• 年卷期：v.16,no.9(September 21, 2012)
• ISSN：1520-586X

文摘

An efficient, scalable synthesis of (鈭?-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (4) is described. Reduction of the pyridinium salt prepared from pyridine and benzyl chloride generated the corresponding tetrahydropyridine derivative. A two-stage epoxidation, followed by ring-opening of the epoxide with BnNH₂, established the regiochemistry of the amino alcohol and served to set the trans-relationship between the amine and the hydroxyl group. The resulting racemic intermediate was then resolved by salt formation with (R)-O-acetyl mandelic acid. The process produced the O-acetyl mandelic acid salt of (鈭?-4 in 27% overall yield from benzyl chloride.