硝酸奥昔康唑的合成工艺改进

Improved Synthesis of Oxiconazole Nitrate

摘要:

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2-氯-1-(2,4-二氯苯基)乙酮(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。

Abstract:

With 1,3-dichlorobenzene as raw materials, 2-chloro-1-(2,4-dichlorophenyl) ethanone (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% to 70.8%, with a purity of 99.9%.The structures of the products were characterized by IR, 1HNMR and HRMS spectra.