沙丁胺醇中两种杂质的合成

Synthesis of two impurities of salbutamol

目的为加强对沙丁胺醇药物的质量控制,合成了欧洲药典中沙丁胺醇的两个杂质。方法分别以4-羟基苯乙酮和3甲-基-4羟-基苯乙酮为起始原料,经溴化、N-苄基叔丁基胺取代,再用H2/Pd-C脱去苄基,最后用硼氢化钠还原合成目标化合物。结果与结论目标化合物结构经1H-NMR、MS确证,合成的两种杂质可以作为沙丁胺醇药物质量控制的杂质对照品。该合成方法反应条件温和,原料易得,操作简单,收率高。

To improve the quality control of salbutamol,two related substances were synthesized.Starting from 4-hydroxy-acetophenone and 4-hydroxy-3-methyl-acetophenone,a convenient synthetic route was designed including bromination,subsititution using N-（tert-butyl）benzylamine,deprotection of benzyl group,and reduction with NaBH4.The raw materials were cheap and easy to obtain and the reaction conditions were mild.The structures of the target compouds were verified by 1H-NMR and MS.The target compounds can be used as the reference substance of the related substances in the quality control of salbutamol.