Method for preparing fenofibric acid by using inorganic alkali as catalyst

Abstract

The invention discloses a method for preparing fenofibric acid by using inorganic alkali as a catalyst, belonging to the field of fenofibric acid catalytic synthesis processes. The method comprises the following steps: by using 4-hydroxyl-4'-chlorobenzophenone, acetone and chloroform as initial raw materials, using sodium hydroxide as a catalyst, and using acetone as a solvent at the same time, performing condensation reaction, and then performing atmospheric distillation, reduced pressure distillation, acidification, filtration and drying to obtain fenofibric acid. The method can be used for greatly reducing the consumption of main raw materials, significantly reducing the production cost of products, and obviously reducing three wastes, so that the method is an efficient and environment-friendly method for synthesizing fenofibric acid, and is suitable for large-scale industrial popularization and application.

Description

technical field [0001] The invention relates to a preparation method of fenofibrate acid, in particular to a method for preparing fenofibrate acid by using an inorganic base as a catalyst, and belongs to the technical field of catalytic synthesis of fenofibrate acid. Background technique [0002] Fenofibric acid is an important intermediate in the synthesis of the blood lipid-lowering drug fenofibrate, and it is widely used. It is usually obtained by condensation reaction using 4-hydroxy-4'-chlorobenzophenone, acetone and chloroform as raw materials. . At present, there have been reports on the preparation of fenofibric acid in China, but the amount of acetone, inorganic alkali, chloroform, and acid is large, and the yield of the crude product is 85%. It needs to be recrystallized with toluene, which has high cost, many wastes, and the solvent has not been effectively treated. , too much salt is not easy to stratify, which affects the follow-up reaction, and the industriali...

AI Technical Summary

Problems solved by technology

At present, there have been reports on the preparation of fenofibric acid in China, but the amount of acetone, inorganic alkali, chloroform, and acid is large, and the yield of the crude product is 85%. It needs to be recrystallized with toluene, which has high cost, many wastes, and the solvent has not been effectively treated. , too much salt is not easy to stratify, which affects the follow-up reaction, and the industrialization is difficult to implement, etc.

[0003] People such as Gu Caixian [synthesis of hypolipidemic drug prozhifen. Pharmaceutical industry, 1983, (6)] take inorganic base as catalyst, adopt 4-hydroxyl-4'-chlorobenzophenone, chloroform, acetone as main raw material, After condensation, distillation, acidification, filtration, recrystallization, and drying, fenofibrate acid is obtained. This method has no specific inorganic base product, and its raw material consumption is large, the product cost is high, and the three wastes are large; Qiao Deyang et al. [TEBA catalytic synthesis Fenofibrate acid. Synthetic Chemistry, 2009,17 (6)] improved above-mentioned method, adopt the potassium hydroxide solution of about 50% as catalyst, with 4-hydroxyl-4'-chlorobenzophenone, chloroform , Acetone is the main raw material, TEBA is the phase transfer catalyst, the whole reaction proceeds smoothly at the liquid-liquid interface, and a certain improvement effect has been achieved, but this method also has the problems of large consumption of raw materials, high product cost, and large wastes, which affect its industrialization Application promotion

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