Synthetic method of environment-friendly and efficient pregabalin

Abstract

The invention relates to a synthetic method of environment-friendly and efficient pregabalin. The synthetic method comprises the following steps: 1) dehydrating and condensing acetate and isopentyl aldehyde to obtain 5-methyl-2-hexenoate; 2) performing cyano addition on the 5-methyl-2-hexenoate to obtain (S)-5-methyl-3-cyanohexanoate; 3) performing hydrogen reduction cyclization on the (S)-5-methyl-3-cyanohexanoate to obtain (S)-4-isobutylpyrrolidin-2-one; and 4) performing hydrolysis and ring opening on the (S)-4-isobutylpyrrolidin-2-one to obtain the pregabalin. The synthetic route has the advantages of cheap and easily available raw materials, few reaction steps, mild process conditions, simple operation, high reaction yield and less environment pollution, and is more suitable for industrial production of bulk drug pregabalin.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical production, and in particular relates to a green and efficient synthesis method of pregabalin. Background technique [0002] Pregabalin is a new type of antiepileptic drug. Its molecular structure has γ-aminobutyric acid structure, so it has anticonvulsant effect. Pregabalin was successfully developed by Pfizer. It was first approved for marketing by the European Medicines Agency (EMA) on July 6, 2004, and then approved by the US Food and Drug Administration (FDA) for marketing on December 30, 2004. In December 2008, the U.S. Food and Drug Administration (FDA) approved pregabalin (trade name "Lyrica") for the treatment of diabetic peripheral neuralgia (DPN) and postherpetic neuralgia (PHN). Most common neuropathic pain. [0003] There are many synthetic routes of pregabalin, which can be mainly divided into three categories: [0004] (1) chemical resolution method: [0005] The chemical...

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Problems solved by technology

[0025] In the above-mentioned synthetic method of pregabalin, malonate or cyanoacetate are commonly used reagents, because the price of this type of reagent is higher, and finally will go through hydrolysis decarboxylation, resulting in poor atom economy, and decarboxylation reaction will be in relatively low temperature simultaneously. The high reaction temperature is completed, and there are many by-products, so that the reaction energy consumption is high and the yield is low; while in the chemical resolution method and the enzymatic resolution method, while obtaining a single isomer, it is necessary to obtain another isomer Racemization, repeated utilization, which makes the method cumbersome to operate and lower the yield

These drawbacks have caused pregabalin process route to be loaded down with trivial details, and production cost increases

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