摘要
探索了用苯甲醛为起始原料合成普利系列血管紧张素转换酶抑制剂(ACEI)药物的前手性中间体2 氧代 4 苯基丁酸(OPBA)的全流程。由苯甲醛与醋酸酐在无水醋酸钾催化下缩合制得肉桂酸、加氢得到苯丙酸、乙酯化后获得苯丙酸乙酯,以苯丙酸乙酯与草酸二乙酯经缩合反应生成中间体3 苄基 2 氧代丁二酸二乙酯,然后经w(H2SO4)=15%的稀硫酸水解制得目标产物OPBA。用正交实验法对合成OPBA的关键步骤苯丙酸乙酯与草酸二乙酯的缩合-水解反应进行了综合优化,得到适宜合成条件为:n(苯丙酸乙酯)∶n(草酸二乙酯)=1∶3;反应温度60℃;缩合时间1 5h;水解时间15h,OPBA产率65%。
The technology of synthesis of 2-oxo-4-phenylbutyric acid(OPBA) from benzaldehyde as prochiral intermediate for preparation of angiotensin converting enzyme inhibitor(ACEI) medicines was studied.Cinnamic acid was firstly prepared by condensation of benzaldehyde with acetic anhydride catalyzed by anhydrous potassium acetate,and then hydrogenated with molecular hydrogen and esterified with ethanol to form ethyl 3-phenylpropionate.Condensation of ethyl 3-phenylpropionate with diethyl oxalate gave diethyl 3-benzyl-2-oxosuccinate,which,by hydrolysis with w(H_2SO_4)=15% aqueous sulfuric acid produced the prochiral intermediate OPBA.The key steps of condensation and hydrolysis were optimized.Thus,with ethyl 3-phenylpropionate and diethyl oxalate in molar ratio 1∶3,duration of condensation 1.5 h at 60 ℃,and time of hydrolysis 15 h,yield of OPBA was 65%.
出处
《精细化工》
EI
CAS
CSCD
北大核心
2004年第7期516-518,共3页
Fine Chemicals
基金
江苏省自然科学基金资助项目(BJ99036)
关键词
2-氧代4-苯基丁酸
苯丙酸乙酯
草酸二乙酯
缩合
水解
2-oxo-4-phenylbutyric acid
ethyl 3-phenylpropionate
diethyl oxalate
condensation
hydrolysis
