改进顺-[2-(2,4-二氯苯基)-2-(1H-咪唑基-1-甲基)-1,3-二氧戊环-4-]对甲苯磺酸酯的合成工艺

Improvement of synthesis of cis-[2-(2,4-Dicholoro-phenyl)-2-(1H-imidazole-1-ylmethyl)-1,3-dioxolane-4-yl] methyl p-toluenesulfonate

目的改进酮康唑的重要中间体顺-[2-(2,4-二氯苯基)-2-(1H-咪唑基-1-甲基)-1,3-二氧戊环-4-]对甲苯磺酸酯的合成工艺。方法以间二氯苯为原料,经过傅-克酰基化、甘油环合、溴代、苯甲酰化、异构体分离、咪唑烷基化、水解、对甲苯磺酰化等八步反应合成目标产物。结果合成的目标化合物的熔点和核磁共振氢谱与相关文献一致,总收率为19.1%。结论改进后的合成工艺条件温和,操作简便,适用于放大制备。

OBJECTIVE To synthesize intermediate of Ketoconazole,cis - [ 2 - （2,4 - Dicholoro - phenyl） - 2 - （ 1H - imidazole - 1 - yl - methyl） - 1,3 - dioxolane -4 - yl ] methyl p - toluenesulfonate. METHODS Target compound was synthesized by steps of Friedel - crafts acylation, glycerol cyclization, bromination, acylation, isomeric separation, imidazole alkylation, hydrolysis and acyla- tion. RESULTS Chemical structure of the title compound and the intermediates was confirmed by ^1HNMR. Total yield was 19. 1%. CONCLUSION This method has the advantages of milder reaction condition, simpler scale - up. It can be applicable to large - scale preparation.