摘要
目的建立混合体系合成雷贝拉唑钠的新方法并对新方法进行优化。方法以2-氯甲基-4-(3-甲氧基丙氧基)-3-甲基吡啶盐酸盐(简称SM1)和2-巯基苯并咪唑(简称SM2)为原料,依据Williamson醚的合成工艺,首先将SM2与氢氧化钠溶液反应得到2-巯基苯并咪唑钠,增强其化学反应活性,接着将SM1与2-巯基苯并咪唑离子在水-乙醇、乙酸乙酯的混合系统中进行化学反应,制得雷贝拉唑硫醚,然后将雷贝拉唑硫醚用二氧化氯氧化制得雷贝拉唑钠粗品,再用重结晶法制备出高纯度的雷贝拉唑钠。结果制备得到的雷贝拉唑钠纯度大于99.7%,收率超过85%,有关物质的总量不大于0.2%,单个杂质不超过0.1%。结论本工艺生产步骤相对较少,减少了其他溶剂的使用,明显降低了生产成本,适合工业化生产,所得产物收率更高,纯度也更高,质量稳定性更好。
Objective:To establish a new one-step synthesis process for rabeprazole sodium and optimize the new process.Methods:The 2-chloromethyl-4-(3-methoxypropoxy)-3-methyl pyridine hydrochloride(SM1 for short)and 2-mercaptobenzimidazole(SM2 for short)are the raw materials.According to the synthesis process of Williamson ether,SM2 was first reacted with sodium hydroxide solution to obtain 2-mercaptobenzimidazole sodium,which enhanced its chemical reactivity,and then SM1 was chemically reacted with 2-mercaptobenzimidazole ion in a mixed system of water ethanol and ethyl acetate to prepare rabeprazole sulfide.Raw rabeprazole sodium was prepared by oxidizing rabeprazole sulfide with chlorine dioxide,and then high-purity rabeprazole sodium was prepared by recrystallization method.Results:The purity of the prepared rabeprazole sodium was over 99.7%,the yield was over 85%,the total amount of related substances was not more than 0.2%,and the single impurity was not more than 0.1%.Conclusion:This method with relatively fewer production steps,reduces the use of other solvents,and significantly reduces production costs.It is suitable for industrial production.The obtained products have higher yield,purity,and quality stability.
作者
冯华
FENG Hua(Medical College,Yueyang Vocational Technical College,Yueyang,Hunan 414000)
出处
《岳阳职业技术学院学报》
2023年第3期76-80,共5页
Journal of Yueyang Vocational and Technical College
基金
2019年度湖南省教育厅科学研究一般项目“雷贝拉唑新晶型原料药合成工艺的优化研究”(19C1864)
2021年度湖南省卫生健康委一般指导课题“缩合与氧化工艺一锅煮制备雷贝拉唑钠及其质量分析”(202113052054)。