均相体系合成苯扎贝特的工艺研究

Synthetic Technology of Benzafibrate in Homogeneous System

以Na OH水溶液代替固体Na OH,在均相体系中合成目标化合物。以BZ收率和含量为指标,考察了Na OH用量和浓度、滴加CHCl3前混合搅拌时间等因素对反应的影响,并通过正交实验得出该工艺的最佳条件。结果表明:当Na OH浓度在55%时,BZ粗品收率和含量分别可由原工艺的95.6%和94.5%提高到98.9%和97.2%,且回收的丙酮不需精馏脱水即可循环使用。该工艺操作简单,避免了严格的无水条件和因Na OH粉碎造成的粉尘污染和腐蚀,更适用于贝特类药物及其相似结构化合物的工业化生产。

Benzafibrate（ BZ）,the hypolipidemic drug,was prepared in homogeneous system with Na OH aqueous solution instead of Na OH solid. Evaluated by the yield and content of BZ,the effect of the concentration and amount of Na OH,the stirring time before the CHCl3 addition were investigated. The optimum conditions of the reaction were obtained by orthogonal experiment. Compared to the original technology,the yield and content of the BZ increased from 95. 6% and 94. 5% to 98. 9% and 97. 2%,respectively,when the reaction occurred in the homogeneous system with 55%（ w / w） Na OH solution. The recovered acetone can be reused without dehydration by distillation. The improved process can be applied to large-scale synthesis of other fibrate drugs and the compounds with similar structure for its simple operation and green technology. The dust pollution and corrosion caused by Na OH grinding together with the strict anhydrous conditions is also avoided.