A kind of preparation method of fenofibric acid

Abstract

The invention discloses a fenofibric acid preparation method. The fenofibric acid preparation method comprises the following steps: (1) stirring and mixing 4-chloro-4'-hydroxybenzophenone and strong alkali in butanone, wherein the stirring is performed under a heating condition for at least 20 minutes; (2) adding a protic solvent into the mixture obtained in the step (1), performing stirring, keeping the temperature, dropwisely adding a butanone solution of 2-bromoisobutyric acid, and then performing a reaction for 2-6 hours; (3) performing posttreatment, and performing separation to obtain a fenofibric acid crude product; and (4) performing refinement to obtain a fenofibric acid refined product. The method is convenient to operate, and does not produce redundant waste as compared with the existing reported process; meanwhile, the method greatly shortens the reaction time and changes the reaction system and the viscosity condition thereof; and the purity of the fenofibric acid prepared by the method disclosed by the invention is higher as compared with a product prepared by the existing reported method, and the purity can be up to 99.5% or above.

Description

Technical field [0001] The present invention belongs to the field of pharmaceutical preparation. Specifically, the present invention relates to a method for preparing fenofibric acid. Background technique [0002] Fenofibrate is currently one of the most commonly used phenoxyester lipid-lowering drugs in clinical practice. Compared with fenofibrate, fenofibric acid is the active substance metabolized in the body, and it has a very high level in the small intestine. Solubilization, therefore increases the bioavailability, and its bioavailability is not affected by food. [0003] There are few reports on the preparation process of fenofibric acid in the published materials, and most of them are condensation or substitution of 4-hydroxy-4'-chlorobenzophenone as the starting material to produce fenofibric acid. Qiao Deyang, Li Gan (Synthetic Chemistry, 2009) described a 50% potassium hydroxide solution as a solvent in TEBA catalytic synthesis of fenofibric acid, 4-hydroxy-4'-chloroben...

AI Technical Summary

Problems solved by technology

[0005] In summary, although the above two routes can obtain relatively satisfactory yields, there are also many defects.

There are following disadvantages in the preparation of fenofibric acid by condensation reaction: 1. Use expensive phase transfer catalyst TEBA or tetra-n-butylammonium bromide; 2. The reaction time is as long as 25h; the reaction is carried out under phase transfer catalytic conditions, which is heterogeneous reaction, not conducive to mass production

However, the substitution reaction to prepare fenofibric acid has the following disadvantages: 1. The reaction time is as long as 16 to 24 hours; big difficulty

[0007] Fenofibric acid has a good market prospect, and the current process reports are not suitable for industrialized production. Therefore, it is very urgent and necessary to find a process suitable for industrialized production of fenofibric acid

Images