摘要
目的研究抗老年痴呆药物重酒石酸卡巴拉汀的合成新工艺。方法以3-羟基苯乙酮为原料,经过成肟反应,Al-Ni合金催化还原,Eschweiler-clarkeN-甲基化反应得重要中间体3-[1-(二甲基氨基)乙基]苯酚,再与另一侧链甲乙氨基甲酰氯连接,合成外消旋的卡巴拉汀,经DDTA拆分,再与酒石酸成盐,最终得到目标产物。结果对卡巴拉汀的合成工艺进行了改进,总产率达4.17%。结论新工艺原料易得,条件温和,收率较高,适合工业生产。
Objective To optimize the synthetic procedure of S- （＋）-rivastigmine hydrogentartrate which was known as an agent for the treatment of Alzheimer disease. Methods S- （＋）-rivastigmine hydrogentartrate was synthesized by using 1- （3-hydroxyphenyl）ethanone as the starting material via oximation, reduction and N-methylation to produce the key which finally reacted with N-ethyl-N-methylcarbamoyl chloride. The enantiomers were resolved with di- （＋）-p-toluoyl-D-tartaric acid, and the title compound was prepared by mixing S-rivastitnnine base with L-（＋）-tartrate. Results The total yield of S-（＋）-rivastigmine hydrogentartrate was 4.17%. Conclusion The materials in this procedure are all commercially available. The reaction conditions are mild and total yield is high.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2007年第2期177-180,共4页
Journal of Southern Medical University
基金
广州市科技计划项目(2005Z3-E5121)
暨南大学科研启动基金(51205008)
