特力利汀关键中间体(2S)-4-氧代-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯的合成研究  

Synthesis of the Key Intermediate(2S)-4-Oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester of Teneligliptin

作　　者：崔哲凯 卓广澜[1] CUI Zhe-kai;ZHUO Guang-lan(Zhejiang Sci-Tech University, College of Science, Hangzhou 310018, China)

机构地区：[1]浙江理工大学理学院,浙江杭州310018

出　　处：《精细化工中间体》2018年第6期36-39,共4页Fine Chemical Intermediates

摘　　要：以4-羟基-L-脯氨酸和半胱胺盐酸盐为起始原料,经过氨基的保护、氧化、缩合3步反应得到合成特力利汀的关键中间体(2S)-4-氧代-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯,总收率73.8%。采用了新的合成策略,对氧化方法进行了研究优化。整体路线环境污染小、对设备腐蚀小、产品收率高,适于工业化推广。其结构经~1H NMR和ESI-MS确证。The key intermediate of Teneligliptin,(2 S)-4-oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester, was synthesized from trans-4-hydroxy-L-proline and cysteamine hydrochloride in three steps including amino protection, oxidation, condensation. The overall yield from this synthetic route was 73.8%. The new strategy used in this method had the advantages including less pollution, lower corrosion, and high yield. It was suitable for industrial application. At the same time, we discussed and optimized the oxidation method. The structure was confirmed by1 H NMR and ESI-MS.

关 键 词：特力利汀中间体 4-羟基-L-脯氨酸 氧化 (2S)-4-氧代-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯 

分 类 号：O624.6[理学—有机化学] R914.5[理学—化学]