甲磺司特合成工艺改进

Improved process for preparing suplatast tosilate

目的研究平喘药甲磺司特的合成工艺。方法以丙烯酸甲酯为原料,经加成、水解和氯代反应得到3-甲硫基丙酰氯;以对硝基苯酚为原料,经成醚、开环及还原反应制得4-(3-乙氧基-2-羟基丙氧基)苯胺,中间体3-甲硫基丙酰氯与4-(3-乙氧基-2-羟基丙氧基)苯胺的酰化产物经对甲苯磺酸甲酯甲基化,制得目标物甲磺司特。结果与结论目标化合物的结构经核磁共振氢谱、元素分析、红外光谱、质谱等确证。简化后的合成工艺,总收率由文献报道的4.5%提高到9.97%(以对硝基苯酚计),该合成路线操作简单,更适合工业化生产。

Aim To improve the synthetic process of suplatast tosilate. Methods One key intermediate 3-meth- ylthiopropionic acid chloride was obtained via addition, hydrolysis, chlorinaion from methyl acrylate;and another key intermediate 4- （3-ethoxyl-2-hydroxylpropoxy） aniline, was obtained via nucleophilic substitution, ring cleavage, nitration, reduction from p-nitrophenol. The acylation product between 3-methylthiopropionic acid chloride and 4- （3-ethoxyl-2-hydroxylpropoxy） aniline was methylated with methyl p-toluenesulfonate to afford the target compound suplatast tosilate. Results and conclusion The structure of target compound was confirmed by ^1H-NMR, elemental analysis, IR and MS. The improved method was easy for synthesis, the overall yield was 9.97 % （caculated with p-nitrophenol）, and suitable for industrial manufacturing.