稳定同位素标记溴布特罗-D_9的合成  

Synthesis of Stable Isotope Labeled of Brombuterol-D_9

作　　者：解龙[1] 王伟[1] 杨超[1] 杜晓宁[1] 杨维成[1] 罗勇[1] 宋明鸣[1] 雷雯[1] 侯捷[1] 涂亚辉 

机构地区：[1]上海化工研究院国家同位素工程技术研究中心-上海分中心,上海200062

出　　处：《化学试剂》2016年第5期468-472,共5页Chemical Reagents

基　　金：科技部十二五重点支撑计划资助项目(2015-BAK45B01-20);上海张江国家自主创新示范区专项发展资金重点资助项目(201505-PT-C101-010)

摘　　要：以叔丁胺-D_9为稳定同位素标记前体,制备目标化合物。以4-氨基苯乙酮为起始原料,经NBS溴化、Cu Br_2溴化后,再与叔丁胺-D_9进行胺化反应,最后使用硼氢化钠还原得到目标化合物。采用均匀设计法对胺化步骤进行研究,实验数据通过二次多项式逐步回归分析,得出了叔丁胺收率最高时各因素组合(胺化反应时间为2.5 h,溶剂三氯甲烷的用量为50 m L,n(叔丁胺-D_9)∶n(4-氨基-3,5-二溴-α-溴代苯乙酮)=2∶1)。目标化合物经过高效液相色谱外标法定量分析,其化学纯度>98.0%,经过质谱检测,其同位素丰度>97.0 atom%D。研制的目标化合物达到了食品安全领域中β-受体激动剂类药物检测用同位素内标试剂的要求。An efficient synthesis of brombuterol-D9 with self-made tert-butylamine-D9 as the isotope labeled precursor has been reported. Brombuterol-D9 was synthesized from 4-aminoacetophenone as the starting material and through the programs of bromination with NBS and CuBr2,amination reaction with tert-butylamine-D9, finally reduction with sodium borohydride. Uniform design method was used to investigate the amination step,the experimental data was analyzed by quadratic polynomial regression to obtained the highest yield of tert-butylamine combination of factors ：the amination reaction time was 2.5 h,the amount of chloroform solvent was 50 mL,the molar feed ratio of tert-butylamine-D9 and 4-amino-3,5-dibromo-cx-bromoacetophenone was 2： 1. Brombuterol-D9 was quantitative analyzed with external standard HPLC, the chemical purity was greater than 98.0% , and the isotopic abundances greater than 97.0 atom% D under the detection with MS. The experimental hrombuterol-D9 has been achieved the isotope internal standard reagent requirements food security in the field of β-agonist class of drugs detected.

关 键 词：同位素标记 溴布特罗-D9 叔丁胺-D9 胺化 还原 

分 类 号：TQ421.6[化学工程]