稳定同位素标记D6-氯丙那林的合成

Synthesis of Isotope-labeled D6-Clorprenaline

摘要:

D6-氯丙那林的合成以邻氯苯乙酮和D6-丙酮为起始原料，邻氯苯乙酮与溴化铜通过溴化反应得到α-溴代邻氯苯乙酮，D6-丙酮经过还原、溴化、胺化、肼解、碱解得到D6-异丙胺，然后α-溴代邻氯苯乙酮和D6-异丙胺通过胺化、还原“一步法”合成得到稳定同位素标记的D6-氯丙那林，以投入的D6-异丙胺的物质的量计算产率为26.2%。目标产物结构经NMR、MS、HPLC和X-ray单晶衍射等表征确认，液相色谱纯度大于98%，液质丰度99.7% atom D，可作为内标试剂用于氯丙那林残留的检测。

Abstract:

D6-clorprenaline was synthesized with D6-acetone (99.9% atom D) and 2'-chloroacetophenone as starting materials. 2'-Chloroacetophenone is brominated by copper bromide to obtain 2-bromo-2'-chloroacetophenone. D6-isopropyl-amine was synthesized by reduction, bromination, amina-tion, hydrazinolysis and alkali hydrolysis reaction with D6-acetone. Then a one-pot method of amination and reduction was designed to synthesize D6-clorprenaline. The yield based on the amount of substance of D6-isopropyl-amine was 26.2%. The structure of target product was confirmed by NMR, MS, HPLC and X-ray crystal diffraction. Its chemical purity was higher than 98%, and isotopic abundance was 99.7% (atom D). The above compound could be used as an internal standard reagent for the determination of residual clorprenaline.