稳定同位素标记妥布特罗-D_9的合成  

Synthesis of Tulobuterol-D_9 Labeled by Stable Isotope

作　　者：黄路敏 杨维成[2,3] 罗勇[2,3] 韩生[1] 杨超[2,3] 解龙 李美华[2,3] 孙雯[2,3] 潘洁[2,3] 

机构地区：[1]上海应用技术学院,上海201418 [2]上海化工研究院,上海200062 [3]国家同位素工程技术研究中心-上海分中心,上海200062

出　　处：《精细化工》2015年第5期561-564,597,共5页Fine Chemicals

基　　金：科技部转制院所专项(2014EG116258);科技部十二五重点支撑计划资助项目(2012BAK25B03-15)~~

摘　　要：以自制的叔丁胺-D9为同位素标记前体,以邻氯苯乙酮为起始原料,溴化后,再与叔丁胺-D9经胺化、硼氢化钠还原后得到稳定同位素标记布特罗-D9。采用均匀设计对胺化步骤进行研究,实验数据通过多元回归分析,得出了优化的工艺条件:反应温度59℃,反应时间5 h,三氯甲烷为25 m L,n(溴代酮)∶n(叔丁胺-D9)=1∶2。目标产物结构经质谱(MS)、核磁(NMR)、高效液相色谱(HPLC)表征,产物纯度高于98.0%,同位素丰度高于97.5%(atom D),可作为食品安全领域检测用同位素内标试剂。This paper presents an efficient synthesis of tulobuterol-D9 with self-made tert-butylamine-D9 as the labeled precursor. Tulobuterol-D9 was synthesized from O-chloroacetophenone as the starting material by bromination with CuBr2, amination with tert-butylamine-Dg, and reduction with NaBH4. Uniform design method was used to study the effects of the process conditions and the experiment data was analyzed by quadratic polynomial regression. The optimized reaction parameters are： reaction temperature is 59 ℃ reaction time is 5 h, dosage of solvent is 25 mL, and the molar ratio of bromoacetophenone to t-butylamine-D9 is 1：2. The as-synthesized product was confirmed by MS, NMR and HPLC to be the target compound. Its chemical purity is higher than 98.0% and isotopic enrichment is higher than 97.5 % （ atom D）. The above compound could be used as internal standard in the field of food safety.

关 键 词：同位素标记 妥布特罗-D9 叔丁胺-D9 胺化 还原 食品与饲料用化学品 

分 类 号：TQ421.6[化学工程]