A Second Generation Synthesis of Benzyl Piperidine Derivatives: A Key Intermediate for the Preparation of SERT/5-HT1A Dual Inhibitor

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• 作者：Atsushi Ueno ; Nobuyuki Ae ; Hideo Terauchi ; Koji Fujimoto ; Yuji Fujiwara
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：August 21, 2015
• 年：2015
• 卷：19
• 期：8
• 页码：1030-1037
• 全文大小：338K
• ISSN：1520-586X

文摘

A second generation process for benzyl piperidine 10 is described. By the use of a Horner鈥揥adsworth鈥揈mmons reaction and selective hydrogenation with Pt/C in ethyl acetate, 2-bromo-5-(hydroxymethyl) phenol 14 was efficiently converted to the compound 10 on a 5 kg scale. A small amount of water was found to be critical to complete the selective hydrogenation with low levels of debrominated byproduct 15. Impurities of the compound 10 were controlled by limiting the quality of 2-bromo-5-(hydroxymethyl) phenol 14 and 1-bromo-2-methoxyethane 15.