西格列汀中间体新合成方法  

New synthetic method of the intermediate of sitagliptin

作　　者：南方梅 刘细建 

机构地区：[1]石家庄以岭药业有限公司,河北石家庄050000 [2]石家庄杏林锐步医药科技股份有限公司,河北石家庄050000

出　　处：《精细与专用化学品》2016年第5期40-43,共4页Fine and Specialty Chemicals

摘　　要：L-门冬氨酸在氯化亚砜作用下选择性甲酯化生成L-门冬氨酸-4-甲酯盐酸盐,经二碳酸二叔丁酯保护氨基,再与N-甲基吗啉,氯甲酸叔丁酯低温下反应,加入硼氢化钠还原,得(3S)-3-(叔丁氧羰基氨基)-4-羟基丁酸甲酯,与对甲基苯磺酰氯反应后的产物继续与格式试剂(2,4,5-三氟苯基)溴化镁、溴化亚铜二甲硫醚反应,经氢氧化钠水解,调酸得化合物Boc-(R)-3-氨基-4-(2,4,5-三氟苯基)丁酸。L-aspartic acid-4-methyl ester hydrochloride was obtained using L-aspartic acid as material by the action of thionyl chloride with selectively esterification.（3S）-3-（tert-butoxycarbonyl-amino）-4-hydroxyl methyl butyrate was got with follow reaction：the protecting amino using tert-butyl dicarbonate,then reacting with methyl N-morpholine,tert-butyl chloroformate under low temperature,reducing reaction using sodium borohydride.The compound Boc-（R）-3-amino-4-（2,4,5-trifluorophenyl）butyric acid was obtained with follow reaction：by reaction using（3S）-3-（tert-butoxycarbonyl-amino）-4-hydroxyl methyl butyrate with p-toluenesulfonyl chloride,than continuting reaction with a Grignard reagent,at last by hydrolysis of lithium hydroxide.

关 键 词：西格列汀 中间体 格式试剂 Ⅱ型糖尿病 

分 类 号：TQ463[化学工程—制药化工]