沙格列汀关键杂质(1R,3S,5R)-3-(氨基羰基)-2-氮杂双环[3.1.0]己烷-2-甲酸叔丁酯的合成  

Synthesis Process of Key Impurity of Saxagliptin(1R,3S,5R)-3-(aminocarbonyl)-2-azabicyclo[3.1.0]hexane-2-carboxylic Acid Tert-butyl Ester

作　　者：张佳佳 杨禹成 诸海滨[1] ZHANG Jia-jia;YANG Yu-cheng;ZHU Hai-bin(School of Chemistry and Chemical Engineering,Southeast University,Jiangsu Nanjing 211189,China)

机构地区：[1]东南大学化学化工学院,江苏南京211189

出　　处：《广州化工》2022年第18期92-93,131,共3页GuangZhou Chemical Industry

摘　　要：对沙格列汀关键杂质(1R,3S,5R)-3-(氨基羰基)-2-氮杂双环[3.1.0]己烷-2-甲酸叔丁酯的合成进行了改进与优化。以(1R,3S,5R)-3-(醇)-2-氮杂双环[3.1.0]己烷-2-甲酸叔丁酯为起始原料,在三氯化钌做催化剂的基础上经高碘酸钠氧化为(1R,3S,5R)-3-(羧酸)-2-氮杂双环[3.1.0]己烷-2-甲酸叔丁酯,然后在乙酸乙酯中与羰基二咪唑反应后,加入氨水在室温搅拌反应3 h,得到目标产物,纯度>99.4%,总收率62.7%。优化后的合成反应条件温和、操作简便。The synthesis of the key impurity of saxagliptin(1 R,3 S,5 R)-3-(aminocarbonyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate tert-butyl ester was improved and optimized.Using(1 R,3 S,5 R)-3-(alcohol)-2-azabicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester as the starting material,using ruthenium trichloride as the catalyst sodium periodate was oxidized to(1 R,3 S,5 R)-3-(carboxylic acid)-2-azabicyclo[3.1.0]hexane-2-carboxylate tert-butyl ester,which was then combined with carbonyl two in ethyl acetate.After the imidazole reaction,ammonia water was added and the reaction was stirred at room temperature for 3 h to obtain the target product with a purity of >99.4% and a total yield of 62.7%.The optimized synthesis reaction conditions were mild and easy to operate.

关 键 词：沙格列汀 关键杂质 质量控制 合成 

分 类 号：O621.3[理学—有机化学]