摘要
提出了一种处理恩替卡韦N8至恩替卡韦反应后处理的新方法。将恩替卡韦N8用二氯甲烷搅拌分散,氮气保护,控制料液温度在-80~-60℃滴加三氯化硼二氯甲烷溶液(1 mol/L)。滴毕,料液升温至-40~-30℃,控制料液温度反应6 h。反应结束后,滴加无水甲醇,降低至。滴毕,降温至-5~0℃搅拌析晶过夜,抽滤,滤饼溶于纯化水中,用6M氢氧化钠调节pH至7.6~7.8,析晶,得到恩替卡韦粗品。该方法操作简单,产品纯度高,成本较低,更适应大批量恩替卡韦的制备生产。
A new method for Entecavir intermediate N8 to prepare Entecavir was established.The Entecavir intermediate N8 was dissolved by dichloromethane,cooling to-80~-60℃.Then,Boron trichloride dichloromethane solution(1 mol/L)was added into the reactor.Start heating to-40~-30℃and then the solution was racted 6 h.When the reaction was finished,CHOH was added into the solution,and then cooling to-5~0℃,the dichloromethane was added.The solution was crystallization overnight,and then filtrated the next day.The filter cake was dissolved in the water and then used sodium hydroxide solution to adjust the pH to 7.6~7.8,crystallization to get Entecavir.The results showed that the purity of the crude product was significantly promoted,the method had the advantages of simple operation and low cost.It would be successfully applied to refine large quantity of Entecavir.
作者
张磊
涂金荣
贺绍杰
苏旭
邹西赢
ZHANG Lei;TU Jin-rong;HE Shao-jie;SU Xu;ZOU Xi-ying(Lianyungang Runzhong Pharmaceutical Co.,Ltd.,Jiangsu Lianyungang 222069,China)
出处
《广州化工》
CAS
2022年第18期76-78,共3页
GuangZhou Chemical Industry
关键词
恩替卡韦N8
恩替卡韦
制备
精制
Entecavir intermediate N8
Entecavir
prepare
refine
