甲磺司特合成工艺改进

: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，制得目标产物甲磺司特。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。

Improved process for preparing suplatast tosilate

Aim To improve the synthetic process of suplatast tosilate. Methods One key intermediate 3-methylthiopropionic 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 . Result 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.