奥扎格雷钠关键中间体对溴甲基肉桂酸甲酯的合成工艺研究  

Synthesis of Methyl p-Bromomethylcinnamate as the Key Intermediate of Ozagrel Sodium

作　　者：马可莹 王渝 陈宇航[1] 黄朋勉[1] MA Ke-ying;WANG Yu;CHEN Yu-hang;HUANG Peng-mian(Changsha University of Science and Technology,College of Chemical and Chemistry Engineering,Changsha 410000,China)

机构地区：[1]长沙理工大学化学化工学院,湖南长沙410000

出　　处：《精细化工中间体》2024年第2期30-33,共4页Fine Chemical Intermediates

基　　金：湖南省教育厅科学研究项目(编号20A019)。

摘　　要：以对甲基苯甲醛和乙酸甲酯为原料,经克莱森施密特缩合反应制备对甲基肉桂酸甲酯。优化条件为:m(乙酸甲酯)∶m(对甲基苯甲醛)=5∶1,n(甲醇钠)∶n(对甲基苯甲醛)=2.0∶1.0,反应温度为65℃,优化条件下对甲基肉桂酸甲酯收率92.32%,含量99.38%;对甲基肉桂酸甲酯与N-溴代丁二酰亚胺(NBS)反应得到奥扎格雷钠的关键中间体对溴甲基肉桂酸甲酯,优化条件为:溶剂为乙酸甲酯,m(乙酸甲酯)∶m(对甲基肉桂酸甲酯)=4∶1,反应温度为70℃,n(N-溴代丁二酰亚胺)∶n(对甲基肉桂酸甲酯)=1.2∶1.0,优化条件下产品收率88.86%,含量97.48%。该法具有绿色环保、收率高、成本低等优势。The intermediate of p-methyl cinnamate was produced by Claisenschmidt condensation reaction with the materials of p-methyl benzaldehyde and methyl acetate.The reaction conditions were optimized as follows:the mass ratio of methyl acetate to p-methylbenzaldehyde was 5∶1,the molar ratio of sodium methanol to pmethylbenzaldehyde was 2.0∶1.0,and the reaction temperature was 65℃.Under the optimized conditions,the yield and content of methyl p-methylcinnamate were 92.32%and 99.38%respectively.The key intermediate of ozagrel sodium was obtained by the reaction of methyl p-methyl-cinnamate with N-bromosuccinimide(NBS).The reaction conditions were optimized as follows:the solvent was methyl acetate,the mass ratio of methyl acetate to methyl p-methylcinnamate was 4∶1,the reaction temperature was 70℃,and the molar ratio of NBS to methyl pmethylcinnamate was 1.2∶1.0.Under optimized conditions the yield and purity of NBS were 88.86%and 97.48%,respectively.The process has the advantages of green environmental protection,high yield and low cost.

关 键 词：奥扎格雷钠 对甲基苯甲醛 对甲基肉桂酸甲酯 对溴甲基肉桂酸甲酯 

分 类 号：R972[医药卫生—药品]