硝酸依柏康唑的合成工艺改进

Improved synthesis of eberconazole nitrate

目的改进硝酸依柏康唑的合成方法。方法以3,5-二氯溴苄为起始原料经Wittig反应、氢化、水解、环合4步反应得到关键中间体2,4-二氯-10,11-二氢-5H-二苯并[a,d]环庚烯-5-酮,该中间体经还原、氯代、氮烃化、成盐4步反应合成硝酸依柏康唑。结果与结论目标化合物的结构经质谱、核磁共振氢谱确证。与原工艺路线相比,改进后的路线反应步骤短、操作简单、条件温和,易于工业化生产,总收率为26%(以3,5-二氯溴苄计)。

Eberconazole nitrate is a topical,broad-spectrum imidazole derivative, effective in pitynasis dermatophytoses and candidiasis. In order to optimize the synthesis of eberconazole nitrate, a new synthetic route was designed. The key intermediate 2,4-dichloro-10,11-dihydro-5H-dibenzo I a, d] cycloheptene-5-one （ 5 ） was synthesized from 3,5-dichloro benzyl bromide via Wittig reaction, hydrogenation, hydrolysis, cyclization. Then, reduction, chlorination, alkylation and salification were combined into one step from the intermediate 5 to eberconazole nitrate. The procedure developed has several advantages such as mild reaction conditions, short process route and easy industrial production. The overall yield of the target compound was 26%.