硝酸奥昔康唑的合成工艺改进

Improved Synthesis of Oxiconazole Nitrate

以1,3-二氯苯为起始原料,经过傅克酰基化、N-烃基化、肟化得到（Z）-2-（1H-咪唑基）-1-（2,4-二氯苯基）乙酮肟（Ⅲ）,中间体Ⅲ再与2,4-二氯氯苄反应,最后与硝酸成盐得到最终产物硝酸奥昔康唑（Ⅰ）。该工艺过程在N-烃基化和肟化时采用＂一釜法＂合成,同时对反应的影响因素进行了优化。与原有工艺相比,优化后的工艺路线简化了操作,并且使硝酸奥昔康唑的总收率由41.8%提高到70.8%,纯度达99.9%（HPLC测得）,产物结构经IR、^1HNMR及HRMS进行了表征。

With 1,3-dichlorobenzene as raw materials,（ Z）-1-（ 2,4-dichlorophenyl）-2-（ 1H-imidazol-1-yl） ethanone hydroxime（ Ⅲ） was synthesized by Friedel-Crafts acylation,N-alkylation and oximation,then it was reacted with 2,4-dichlorobenzyl chloride and salinized by nitric acid,and got the final product oxiconazole nitrate（ Ⅰ）. The N-alkylation and oximation were performed by a ＂ one-pot ＂ reaction,and the key factors of the reaction were investigated. The improved synthetic route simplified the operation procedure,and the overall yield of oxiconazole nitrate was increased from 41. 8% to70. 8%,with a purity of 99. 9%. The structures of the products were characterized by IR,^1HNMR and HRMS spectra.