卡培他滨关键中间体精制工艺改进

目的：针对卡培他滨关键中间体精制收率低,周期长等问题,对精制工艺进行优化。方法先将卡培他滨中间体乙酸乙酯提取液稀释至一定浓度,再于适宜温度下沉淀杂质,经过适宜的陈化时间后,过滤去除杂质,母液浓缩后进行结晶。结果将卡培他滨中间体乙酸乙酯提取液稀释至56～60 g·L －1,于0～2℃析晶,陈化12～14 h 后,滤除杂质,母液经浓缩、脱色后浓度调节至85～90 g·L －1,于－6～－3℃析晶,陈化8～12 h 后,过滤,滤饼于60℃真空干燥至恒重,即得到纯度99．5％以上的卡培他滨关键中间体。结论该精制工艺过程简便、具有分离效率高、收率高、成本低廉的优势,尤其适合于工业化生产。

Purification techniques of key intermediate of kapecitabine

Objective The purification process of the key intermediate of kapecitabine was improved in order to solve the problems of low yield and long period.Method Firstly,the ethyl acetate extract of the key intermediate of kapecitabine was diluted to a certain concentration,and the impurities precipitated out at the appropriate temperature Finally,the impurities were filtered off after aging,and the mother liquid was concentrated and crystallized.Results The ethyl acetate extract of key intermediate of kapecitabine was diluted to 56 ~60 g·L -1 ,crystallized at 0 ~2 ℃,and aged for 12 ~14 h.Then impurities was filtered off,and mother liquor was concentrated and decolored.The concentration was adjusted to 85 ~90 g·L -1 ,crystallized at -6 ~-3 ℃,and aged for 8 ~12 h.After filtration, the filter cake was dried at 60 ℃ under vacuum to constant weight.The key intermediate of kapecitabine was obtained with purity higher than 99.5%.Conclusions The purification process is simple with high separation efficiency and high yield,which is cost saving and particularly suitable for industrial production.