一种替格列汀关键中间体的合成方法  

A Method for Synthesis of Key Intermediate of Teneligliptin

作　　者：张振科 高尤剑 ZHANG Zhen-ke;GAO You-jian(Zhejiang Shaxing Technology Co.,Ltd.,Linhai 317000,China)

机构地区：[1]浙江沙星科技有限公司,浙江临海317000

出　　处：《化工管理》2022年第28期161-163,共3页Chemical Engineering Management

摘　　要：该工艺以L-羟基脯氨酸(HYP)为起始原料,制备了替格列汀关键中间体(2S)-4-氧代-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯(TES)。该过程首先通过酯化反应得到(2S,4R)-4-羟基-L-脯氨酸甲酯(TES-1),然后二碳酸二叔丁酯(Boc)保护得到(2S,4R)-N-Boc-4-羟基-L-脯氨酸甲酯(TES-2),经次氯酸钠/四甲基哌啶氮氧化物(TEMPO)体系氧化得到Boc-4-氧代-L-脯氨酸甲酯(TES-3),最后通过氨酯交换得到目标产物TES。The key intermediate(2S)-4-oxy-2-(3-thiazolylcarbonyl)-1-pyrrolidine carboxylate of Teneligliptin was prepared from L-hydroxyproline(HYP)as starting material.In this process,(2S,4R)-4-hydroxy-L-proline methyl ester(TES-1)was f irstly obtained by esterif ication,and then(2S,4R)-N-BOC-4-hydroxy-L-proline methyl ester(TES-2)was obtained by TEMPO-mediated oxidation with sodium hypochlorite/tetramylpiperidine nitrogen oxide(TEMPO).Finally,the target product(2S)-4-oxy-2-(3-thiazolyl carbonyl)-1-pyrrolidine carboxylate tert-butyl ester(TES)was obtained by transesterif ication with Boc-4-oxy-L-proline methyl ester(TES-3).

关 键 词：替格列汀 (2S)-4-氧代-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯 合成 L-羟基脯氨酸 

分 类 号：TQ463.5[化学工程—制药化工]