维达列汀的合成工艺改进  

Improved Synthesis of Vildagliptin

作　　者：韩春明[1,2] 殷剑[3] 王风云[1] 雷武[1] 夏明珠[1] 朱其军 

机构地区：[1]南京理工大学工业化学研究所,江苏南京210094 [2]盐城格瑞茵化工有限公司,江苏盐城224400 [3]南昌工学院民族教育学院,江西南昌330108

出　　处：《精细化工》2015年第1期69-72,共4页Fine Chemicals

摘　　要：以L-脯氨酸及盐酸金刚烷胺为起始原料,L-脯氨酸经氯乙酰基化,羰基二咪唑催化氨化,脱水反应生成(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈;盐酸金刚烷胺先被混酸硝化,再在碱性条件下水解得3-羟基金刚烷胺,然后与(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈反应生成维达列汀。整条路线原料简单易得,步骤较少,操作简单,反应条件温和,维达列汀的总收率从32%提高到42%,产物纯度在99%以上,产物结构经核磁,红外和质谱进行了表征。（S）-1-（2-Chloroacetyl） pyrrolidine-2-carbonitrile was synthesized from L-proline via successive reactions with chloro-acetyl chloride,ammoniated by 1,1＇-carbonyldiimidazole with ammonium bicarbonate and dehydrated by phosphorus oxychloride;3-aminoadamantanol was synthesized from 1-adamantanamine hydrochloride which was previously nitrified by mixed acids,and then was replaced by alkali.This intermediate reacted with（S）-1-（2-chloroacetyl） pyrrolidine-2-carbonitrile to produce the target compound vildagliptin.The entire route is characterized by simple and easy access to raw materials,fewer steps,facile operation,and mild reaction conditions.The total yield of vildagliptin was increased from 32% to 42%,with a purity of more than 99%.The structure of product was characterized by means of IR,^1HNMR and MS.

关 键 词：(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈 3-羟基金刚烷胺 维达列汀 医药与日化原料 

分 类 号：R914[医药卫生—药物化学]