沙丁胺醇-D_2的合成  

Synthesis of Albuterol-D_2

作　　者：徐建飞[1] 卢伟京[1] 颜彰伟[1] 罗勇[1] 杜晓宁[1] 

机构地区：[1]上海化工研究院稳定性同位素研究所,上海200062

出　　处：《精细化工》2013年第10期1198-1200,共3页Fine Chemicals

基　　金：上海市科委基地能力提升专项(11DZ2210700);上海化学试剂产业技术创新战略联盟(11DZ0511700-LMCY-5)~~

摘　　要：以水杨醛和溴乙酰氯为原料,经Friedel-Crafts酰基化制备得到5-溴乙酰基-2-羟基苯甲醛(Ⅱ),再与叔丁胺胺化和盐酸水解,过柱纯化后得到中间体5-{[(1,1-二甲基乙基)氨基]乙酰基}-2-羟基苯甲醛盐酸盐(Ⅲ),化合物Ⅲ再用硼氘化钠还原制得目标产物沙丁胺醇-D2(Ⅳb)。合成路线优势在于最后一步反应引入氘代同位素,保证氘代物丰度的不稀释,且操作简单,工艺流程短,副产物少,收率可达70%以上。产品经MS和1HNMR表征和确认,氘标记同位素丰度>97.1%。Friedel-Crafts acylation of salicylaldehyde with bromoacetyl chloride afforded 5- （bromoacetyl）-2-hydroxybenzaldehyde（ Ⅱ ）, which then went through amination with tert-butylamine and acid hydrolysis. After going through the purification column the intermediate 5-t [ （1, 1- dimethylethyl） amino ] acetyl t -2-hydroxybenzaldehyde hydrochloride （ Ⅲ ） was obtained. The target compound albuterol-D2 （Ⅳb） was obtained by reduction with boron sodium deuteride. The advantage of this synthetic route lies in the last step of the reaction, where deuterium isotope was introduced to ensure that deuterium labeled isotope abundance was not diluted. The synthetic route boasts the advantages of simple operation, short process flow, and less side product. The yield was more than 70%. The product was characterized by means of MS and l HNMR, and the deuterium enrichment was more than 97.1%

关 键 词：酰基化 叔丁胺 氘代 沙丁胺醇-D2 精细化工中间体 

分 类 号：R974[医药卫生—药品]