氟康唑的合成工艺研究及优化

目的 研究高效广谱抗真菌药物氟康唑的合成路线并优化其工艺。方法 以间二氟苯为起始原料，经酰基化、烷基化、环氧化、缩合得氟康唑，并考察各步的反应原理和影响因素。结果与结论 第一步采用无溶剂法；第二步以甲苯为溶剂，最佳投料比m（酰化产物） : m（NaHCO3）: m（1H-1,2,4-三氮唑）= 1 : 2 : 1，以PEG-600为相转移催化剂，回流反应5 h；第三、四步“一锅煮”为最优工艺条件。该路线条件温和，原料廉价易得，成本低，产物纯度高，总收率（56%）远高于相关报道路线,适合工业化生产。

Optimization and study on the synthesis of fluconazole

We focus on optimizing the process route of fluconazole with potent and broad-spectrum antifungal activities.In the study,fluconazole was prepared via Friedel-Crafts acylation,alkylation,epoxidation and condensation reaction.What′s more,the mechanism and influencing factors of the procedure was investigated.According to the results of our study,we finally established the appropriate and viable method.Firstly,the m-difluorobenzene as starting material was reacted with chloroacetic chloride without other dissolvent to give intermediate acylated m-difluorobenzene,then it was refluxed with sodium bicarbonate and 1H-1,2,4-trizole for 5 h in the presence of toluene and PEG-600,finally after one pot epoxidation and condensation procedure,the target compounds was synthesized.The total synthesis was mild,economical and with high purity in 56% yield much higher than that of reported routes.