摘要
目的:改进苯磺顺阿曲库铵重要中间体R-四氢罂粟碱-N-乙酰-L-亮氨酸盐精制方法。方法:以3,4-二甲氧基苯乙胺、3,4-二甲氧基苯乙酸为起始物料,经缩合、环合、加氢得四氢罂粟碱,后经拆分、精制得R-四氢罂粟碱-N-乙酰-L-亮氨酸盐。结果:目标产物收率为24.0%以上,R对映体含量达99.5%以上。结论:本工艺操作简便,产品纯度和收率较高,适于大批量生产。
Objective:To improve the refining method of R-tetrahydropapaverine-N-acetyl-L-leucine salt,an important intermediate of cisatracurium besylate.Methods:Using 3,4-dimethoxyphenethylamine and 3,4-dimethoxyphenylacetic acid as starting materials,tetrahydropapaverine is obtained by condensation,cyclization,and hydrogenation,which is resolved by a resolving agent.R-tetrahydropapaverine-N-acetyl-L-leucine salt is obtained after resolution and purification.Results:The yield of the target product is over 24.0%,and the content of R-enantiomer is over 99.5%.Conclusion:The process is easy to operate and suitable for mass production with high purity and yield.
作者
周亚兵
汪晓铭
杜芳
张建忠
ZHOU Yabing;WANG Xiaoming;DU Fang;ZHANG Jianzhong(SPH Dongying(Jiangsu)Pharmaceutical Co.,Ltd.,Jiangsu Nantong 226010,China;Shanghai Pharmaceuticals Holding Co.,Ltd.,Shanghai 200020,China)
出处
《上海医药》
CAS
2020年第23期105-109,共5页
Shanghai Medical & Pharmaceutical Journal
基金
上海市“科技创新行动计划”生物医药领域产学研医合作项目(项目编号:16DZ1911101)。
