摘要
以市场易得的4-AA和2-重氮乙酰乙酸对硝基苄酯为原料,先将2-重氮乙酰乙酸对硝基苄酯与三甲基碘硅烷反应得到烯醇硅醚化物,再与4-AA进行aldol反应,不经分离直接水解得到化合物(5),最后经卡宾环合反应得到亚胺培南母核,即4-硝基苄基-(5R,6S)-6-[1R]-1-羟基乙基]-3,7-二酮-1-氮杂双环[3.2.0]庚烷-2-羧酸酯,产物结构经1H-NMR和MS进行确认,以4-AA计总收率达83%。该法合成亚胺培南母核产品收率和纯度高,操作简单,适合工业化生产。
Starting from 4-AA and p-nitrobenzyl 2-diazoacetoacetate,imipenem mother nuclide,p-nitrobenzyl-(5R,6S)-6-[1R]-(1-hydroxyethyl)-3,7-dione-1-azabicyclo(3.2.0)heptane-2-carboxylate,was synthesized in 3 steps.Firstly,aldol reaction was performed between 4-AA and silyl enol ether product of p-nitrobenzyl 2-diazoacetoacetate and trimethylsilyl iodide,then a direct hydrolysis reaction was followed without separation,and finally,carbene cyclization reaction was conducted.The chemical structure of the product was confirmed by 1H-NMR and MS,and the total yield was 83%based on 4-AA.The preparation method has advantages of high yield and purity of the product,simple operation and suitable for industrial production.
作者
徐旋
徐龙
章玉华
谢万喜
李刘彬
XU Xuan;XU Long;ZHANG Yu-hua;XIE Wan-xi;LI Liu-bin(Zhejiang Hisoar Chuannan Pharmaceutical Co.,Ltd.,Linhai,Zhejiang 317016,China)
出处
《浙江化工》
CAS
2018年第3期8-11,共4页
Zhejiang Chemical Industry
