富马酸泰诺福韦酯合成工艺改进  

Synthesis technology improvement of tenofovir disoproxil fumarate

作　　者：万晓辉[1] 石昕[1] 

机构地区：[1]青岛职业技术学院生物化工学院,青岛266555

出　　处：《实用药物与临床》2013年第9期828-829,共2页Practical Pharmacy and Clinical Remedies

摘　　要：目的探寻简单易操作的富马酸泰诺福韦酯的合成工艺。方法以(R)-1,2-丙二醇为起始原料,经过酯化和氮烃化、氧烃化、水解、成酯和成盐5步合成富马酸泰诺福韦酯。将亚磷酸二乙酯与多聚甲醛反应,然后用对甲苯磺酰氯进行酰化,制备甲苯磺酰氧甲基膦酸二乙酯。结果改进后的合成路线更短,反应条件温和,总收率达到27.1%。结论改进后的工艺简单,易于操作。Objective To explore the easily operated synthetic process of tenofovir disoproxil fumarate.Methods Tenofovir disoproxil fumarate was synthesized from（R）-1,2-Propanediol by condensation,N-alkylating,O-alkylating,hydrolysis,esterification and salification.P-toluene sulfonic acid diethoxyphosphorylmethylester was prepared from diethyl phosphite and paraformaldehyde by condensation,esterification and by acylation of toluene sulfonyl chloride.Results The technique was improved successfully due to the shorter synthetic route,simple technology under mild conditions.The newtechnology was for industrialization with an overall yield of about 27.1%.Conclusion The improved technology is simple and easy to operate.

关 键 词：富马酸泰诺福韦酯 合成工艺 改进 

分 类 号：TQ463[化学工程—制药化工]