丁酸氯维地平的合成工艺

Technological improvement of synthesis for clevidipine butyrate

目的研究适合工业化生产的丁酸氯维地平合成方法。方法采用2,3-二氯苯甲醛、β-氨基巴豆酸甲酯与乙酰乙酸乙酯环化缩合,选择性水解得到4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸单甲酯钾盐,再同丁酸氯甲酯反应得到丁酸氯维地平。结果该合成工艺的丁酸氯维地平总收率为48%。结论该工艺稳定,操作简单,适合工业化生产丁酸氯维地平。

Objective To investigate the industrialization method for clevidipine butyrate.Methods Clevidipine butyrate was synthesized after several processes,including cyclocondation of 2,3-dichlorobenzalde-hyde,methyl β-aminobutenate and ethyl acetoacetate,selective hydrolysis through which 4-（2,3-dichloro-pheny1）-1,4-dihydro-2,6-dimethy-3,5-pyridinedicarboxylic acid monomethyl ester potassium salt was obtained,and reaction with chloromethy butyrate.Results The total yeild rate of clevidipine butyrate was 48%.Conclusion This method was simple and reproducible,and this synthesis route is suitable for the commercial production of clevidipine butyrate.