(1R,5S,6r)-6-甲酰基-3-氮杂双环[3.1.0]己烷-3-羧酸叔丁酯的合成  

Synthesis of (1R,5S,6r)-6-formyl-3-azabicyclo[3.1.0] Hexane-3-carboxylic Acid Tert-butyl Ester

作　　者：杨葵华[1] 何冀川[1] 魏娜 YANG Kuihua;HE Jichuan;WEI Na(School of Chemistry and Chemical Engineering,Mianyang Teachers'College,Mianyang,Sichuan 621000)

机构地区：[1]绵阳师范学院化学与化学工程学院,四川绵阳621000

出　　处：《绵阳师范学院学报》2022年第11期49-57,共9页Journal of Mianyang Teachers＇ College

摘　　要：针对(1R,5S,6r)-6-甲酰基-3-氮杂双环[3.1.0]己烷-3-羧酸叔丁酯的合成过程,采用两条路线进行研究和分析.第一条路线以N-Boc-3-吡咯啉为原料与重氮乙酸乙酯发生环丙烷化反应,再经还原、氧化成(1R,5S,6r)-6-甲酰基-3-氮杂双环[3.1.0]己烷-3-羧酸叔丁酯.第二条路线是以氯乙酸乙酯和富马酸二乙酯作为原料发生迈克尔加成反应,再用醋酸酐反应制得五元环,最后经脱苄上Boc制得(1R,5S,6r)-6-甲酰基-3-氮杂双环[3.1.0]己烷-3-羧酸叔丁酯.在制备过程中各个中间体均采用薄层色谱、液相色谱和核磁共振氢谱等分析手段验证结构.最后根据步骤、原材料价格、耗时以及产率的对比,得出适合工业生产的最优方案.The synthesis of(1 R, 5 S, 6 r)-6-formyl-3-azabicyclo [3.1.0] hexane-3-carboxylate tert-butyl ester was studied and analyzed by two methods. In the first route, N-Boc-3-pyrroline was used as raw material to undergo cyclopropanation with ethyl diazoacetate, and then reduced and oxidized to(1 R, 5 S, 6 r)-6-formyl-3-azabicyclic [3.1.0] hexane-3-carboxylate tert-butyl ester. In the second route, Michael addition reaction was performed with ethyl chloroacetate and diethyl fumarate as raw materials, followed by acetic anhydride reaction to produce five-membered ring, andby removing the benzyl group and then adding Boc to prepare(1 R, 5 S, 6 r)-6-formyl-3-azabicyclo [3.1.0]hexane-3-carboxylic acid tert-butyl ester. In the preparation process, the structures of each intermediate were verified by TLC, LC and 1 H NMR. Finally, according to the comparison of steps, raw material prices, time consumption and yield, the optimal scheme suitable for industrial production is obtained.

关 键 词：含氮杂环 药物中间体 有机合成 

分 类 号：O626.1[理学—有机化学]