维格列汀重要中间体合成工艺研究  

Study on the Synthes of Vildagliptin Intermediate

作　　者：郭丽媛[1] 董志艳[1] 黄胜堂[1] 吴诗[1,2] 

机构地区：[1]湖北科技学院药学院,湖北咸宁437100 [2]湖北科技学院糖尿病心脑血管病变湖北省重点实验室

出　　处：《湖北科技学院学报（医学版）》2017年第3期185-187,190,共4页Journal of Hubei University of Science and Technology(Medical Sciences)

基　　金：湖北科技学院药学重点学科专项科研项目(2016-18XZY07);湖北科技学院糖尿病专项(ZX1016)

摘　　要：目的重点考察不同的反应条件对目标化学物收率的影响。方法以L-脯氨酸为起始原料,用氯乙酰酰化、二碳酸二叔丁酯催化酰胺化、三氟乙酸酐(TFAA)脱水三步反应,得到目标化合物(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈。结果在氯酰化反应中当n(氯乙酰氯)∶n(L-脯氨酸)=1.8∶1、反应时间2.5h时为最适条件,反应收率87%;在酰胺化反应中n[(S)-1-(2-氯乙酰基)吡咯烷-2-甲酸]:n(NH4HCO3)=1∶4.5,且室温下反应为最适条件,反应收率76.5%;脱水反应时,n[(S)-1-(2-氯乙酰基)吡咯烷-2-甲酰胺]∶n(TFAA)=1∶2,反应时间为2h为最适条件,反应收率为89.2%。结论优化后目标产物三步总收率为59.36%,效果较好。Objective The effects of different reaction conditions on the yield of the target compound were investigated. Methods（ S）-1-（ 2-chloroacetyl） pyrrolidine-2-carbonitrile was synthesized from L-proline via successive reactions with chloro-aeetyl chloride,ammoniated by di-tert-butyl dicarbonate with ammonium bicarbonate and dehydrated by trifluoroacetic anhydride（ TFAA）. Results Some factors were studied,which showed that the best yield of acylation reaction was obtained when the reaction time is 2. 5 hours,with 1. 8 ∶ 1ratio of chloracetyl chloride to the L-proline,the yield was 87%; The best yield of amidation was obtained at room temperature,with 1∶ 4. 5 ratio of（ s）-1-（ 2-chloro acetyl） pyrrolidine-2-formic acid to NH4HCO3,the yield was 76. 5%; And the best yield of dehydration reaction was obtained when the reaction time is 2 hours,with 1∶2 ratio of（ S）-1-（ 2-chloroacetyl） pyrrolidine-2-carboxamide to TFAA,the yield was 89. 2%. Conclusion Finally,the overall yield was 59. 36%,the effect is well.

关 键 词：维格列汀 (S)-1-(2-氯乙酰基)吡咯烷-2-甲腈 中间体 合成 

分 类 号：R963[医药卫生—微生物与生化药学]