第 36 卷第 4 期 Vol. 36 No. 4 2006 年 8 月 Aug 2006

所属栏目：医药及中间体 11βHSD1抑制剂1-(4-氟苯甲酰基)-4-(4-三氟甲氧基苯甲酰基)哌啶的合成

刘瑛; 马啸华; 郝景山(河南商丘师范学院化学系; 河南夏邑第二高级中学; 河南商丘; 河南夏邑)

摘　要：以4-甲氧羰基哌啶盐酸盐(2)和氟苯甲酰氯(3)为起始原料,在三乙胺的作用下以93.5%的收率制得化合物4;化合物4甲醇水溶液,在弱碱氢氧化锂作用下,以97.8%的收率水解为化合物5;化合物5在羰基二咪唑与N-甲基-N-甲氧基盐酸盐(6)作用,以94.6%的收率制得化合物7;化合物7和4-三氟甲氧基苯基溴化镁(8)偶联,以71.8%的收率制得化合物1。四步反应总收率62.1%。

关键词：哌啶衍生物; 11βHSD1抑制剂; 合成

中图分类号：TQ463+.54　　文献标识码：A　　文章编号：1009-9212(2006)04-0021-03

Synthesis of 11βHSD1 Inhibitors 1-(4-Fluorobenzoyl)-4-(4-trifluromethoxylbenzoyl)piperidine

LIU Ying1; MA Xiao-hua1; HAO Jing-shan2 （1. Department of Chemistry; Shangqiu Normal University; Shangqiu 476000; China; 2 . Xiayi No.2 High School; Xiayi 476400; China）

Abstract：A Practical synthesis method of 1-(4-fluorobenzoyl)-4-(4-trifluoromethoxylbenzoyl)piperidine 1 was described. 4-Flurobenzoyl chloride 3 was treated with 1.5 equiv. of methylisonipecotate 2 in DCM in the presence of triethylamine to form compound 4 in 93.5% yield. The compound 4 then treated with aqueous LiOH to produce 5 in 97.8% yield. After the compound 5 was converted into 7 in 94.6% yield,the compound 7 then coupled with Grignard agent of compound 8 to obtain compound 1 in 71.8% yield. The overall yield...

Key words：piperidine derivative; 11βHSD1 inhibitors; synthesis

收稿日期：2006-06-30

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