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

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

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%。

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 of four steps was 62.1%.