抗真菌原料药泊沙康唑的合成工艺改进  

Improvement in the Synthesis Process of Antifungal Bulk Drug Posaconazole

作　　者：邢丽华 王艳峰 XING Lihua;WANG Yanfeng(School of Resources,Environment and Architectural Engineering,Chifeng University,Chifeng,Neimenggu 024000,China;Youcare Pharmaceutical Group Company,Beijing 100176,China)

机构地区：[1]赤峰学院资源环境与建筑工程学院,内蒙古赤峰024000 [2]悦康药业集团股份有限公司,北京100176

出　　处：《浙江化工》2024年第9期30-37,共8页Zhejiang Chemical Industry

基　　金：内蒙古自治区高等学校科学技术研究项目(NJZY22175)。

摘　　要：目的:设计一条新的、适合工业化生产的泊沙康唑合成工艺路线。方法:以4-(4-(4-硝基苯基)-1-哌嗪基)苯酚为起始原料,分别与4种羟基保护基试剂反应,然后依次经硝基还原、缩合、关环、还原反应得到泊沙康唑。结果:采用乙酰氯、3,4-二氢-2H-吡喃、三苯基氯甲烷、氯化苄4种试剂作为羟基保护基,反应总收率分别为46.93%、40.41%、36.73%、20.17%。结论:采用乙酰氯作为羟基保护基合成泊沙康唑的工艺,可以避免引入含有苯环或吡喃环的杂质,从源头上保证了产品的质量。该工艺具有路线短、总收率高、质量可控等优点,为工业化生产奠定良好基础。Objective:To design a new synthetic process route of posaconazole suitable for industrial production.Methods:4-(4-(4-nitrophenyl)-1-piperazinyl)phenol was used as starting material to react with four hydroxyl protective group reagents,and then posaconazole was obtained by nitro-reduction,condensation,cyclization and reduction.Results:Four reagents including acetyl chloride,3,4-dihydro-2H-pyran,triphenylchloromethane and benzyl chloride were used as hydroxyl protective group,and the total reaction yields were 46.93%,40.41%,36.73%,and 20.17%,respectively.Conclusion:The synthesis process of posaconazole using acetyl chloride as hydroxyl protective group can avoid the introduction of impurities containing benzene or pyran rings,and ensure the product quality from the source.This process has the advantages of short route,high total yield and controllable quality,laying a good foundation for industrial production.

关 键 词：泊沙康唑 合成 乙酰氯 羟基保护基 

分 类 号：TQ460.6[化学工程—制药化工]