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%。 Using salicylaldehyde and bromoacetyl chloride as raw materials, 5-bromoacetyl-2-hydroxybenzaldehyde (Ⅱ) was obtained by Friedel-Crafts acylation. Amination with tert-butylamine and hydrochloric acid gave the intermediate 5 - {[(1,1-dimethylethyl) amino] acetyl} -2-hydroxybenzaldehyde hydrochloride (III) and compound III was reduced with sodium borodeuteride to obtain the target product albuterol-D2 IVb). The advantage of the synthesis route lies in the fact that the last step reaction introduces deuterated isotope to ensure undiluted abundance of deuteride and has simple operation, short process flow and less by-products, and the yield can reach more than 70%. The product was characterized and confirmed by MS and 1H NMR. Deuterium labeled isotope abundance> 97.1%.