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目的为加强对溴丙胺太林原料药的质量控制,合成溴丙胺太林杂质A以作为对照品使用。方法以呫吨酸(3)为起始原料,采用两条合成路线合成关键中间体9-羟基丙胺太林:1)首先氧化引入羟基,然后再经过甲酯化和酯交换反应得到9-羟基丙胺太林;2)首先进行酯化反应,再经过氧化反应引入羟基得到9-羟基丙胺太林。最后经过季铵盐化反应得到终产物。结果与结论相比第一条合成路线,第二条路线更简短,收率更高。目标化合物结构经1H-NM R、13C-NM R和M S确证,HPLC检测纯度达到98%以上,合成的杂质可以作为溴丙胺太林原料药质量控制的杂质对照品。
Objective To strengthen the quality control of raw materials of bromopropylamine too forest, synthesis of bromopropylamine too forest impurity A as a reference substance to use. Methods The key intermediates 9-hydroxypropylamine were synthesized by two synthetic routes using xanthic acid (3) as the starting material: 1) the hydroxyl groups were first oxidized and then the methyl ester and transesterification gave 9-hydroxy Propyl amine too forest; 2) The first esterification reaction, and then through the oxidation reaction to hydroxyl 9-hydroxypropylamine too forest. Finally, quaternary ammonium reaction to get the final product. The first synthetic route is compared with the conclusion, the second route is shorter and the yield is higher. The structure of the target compound was confirmed by 1H-NM R, 13C-NM R and M S, and the purity of the target compound was over 98% by HPLC. The synthesized impurities could be used as impurity reference substance for the quality control of bromopropamid.