Preparation method of gemfibrozil

Abstract

The invention provides a preparation method of gemfibrozil. The preparation method is characterized by comprising the following steps: carrying out a salt-forming reaction between starting materials, namely 2,5-dimethylphenol and diethyl malonate, under the action of alkali; carrying out a nucleophilic substitution between the reaction product and 1,3-dibromopropane; hydrolyzing in an aqueous solution of alkali and carrying out a decarboxylation reaction to generate 5-(2,5-dimethylphenoxyl)pentanoic acid; and carrying out a methylation reaction between the reaction product and dimethyl sulphate (V) under the action of alkali so as to generate gemfibrozil. The preparation method has simple processing steps, reaction conditions are not harsh, synthesis route has no special requirements on equipment, investment cost of production equipment is greatly reduced, and it is easy to realize industrial production. The raw materials are easily available in the market, and cost is relatively low. Thus, industrial cost reduction is realized.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a preparation method of gemfibrozil. Background technique [0002] Gemfibrozil (Gemfibrozil) chemical name is 2,2-dimethyl-5-(2,5-dimethylphenoxy) valeric acid, which belongs to clofibrate derivatives blood lipid regulating drugs, and was introduced by the United States in 1982 Years of development and listing. It is suitable for patients with severe type Ⅳ or Ⅴ hyperlipoproteinemia, high risk of coronary heart disease, but diet control, weight loss and other treatments are ineffective. The drug can be used to prevent arteriosclerosis, and help reduce the incidence of myocardial infarction, with less toxic side effects. [0003] Description of the closest scheme: Condensation reaction of 2,5-xylenol (1) with 5-halo-2,2-dimethylpentanoate in the presence of a base under the action of a phase transfer catalyst, followed by addition of a base Carry out the hydrolysis...

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Problems solved by technology

[0003] Explanation of the closest scheme: Condensation reaction of 2,5-xylenol (1) with 5-halo-2,2-dimethylvalerate in the presence of a base under the action of a phase transfer catalyst, followed by addition of base Carry out the hydrolysis reaction to obtain the product gemfibrozil, as shown in the following process route, the main deficiency in this process route is: the raw material (2) is unsuitable to obtain, the price is higher, and the actual production cost increases;

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