A green and efficient synthetic method of pregabalin

Abstract

The invention relates to a green and efficient method for synthesizing pregabalin, which includes: 1) dehydration condensation of acetate and isovaleraldehyde to obtain 5-methyl-2-hexenoate; 2) 5-methyl-2- Hexenoate ester undergoes cyano addition to obtain (S)-5-methyl-3-cyanocaproate; 3) (S)-5-methyl-3-cyanocaproate is reduced by hydrogen to form a ring Obtain (S)-4-isobutylpyrrolidin-2-one; 4) (S)-4-isobutylpyrrolidin-2-one is hydrolyzed to obtain pregabalin. This synthesis route has cheap and easily available raw materials, few reaction steps, mild process conditions, simple operation, high reaction yield, and low environmental pollution, and is more suitable for the industrial production of the raw material drug pregabalin.

Description

Technical field [0001] The invention belongs to the technical field of pharmaceutical production, and specifically relates to a green and efficient method for synthesizing pregabalin. Background technique [0002] Pregabalin is a new type of anti-epileptic drug. Its molecular structure has a gamma-aminobutyric acid structure, so it has anti-convulsant effects. Pregabalin was successfully developed by Pfizer and was first approved for marketing by the European Medicines Agency (EMA) on July 6, 2004, and then by the U.S. Food and Drug Administration (FDA) on December 30, 2004. In December 2008, the U.S. Food and Drug Administration (FDA) approved pregabalin (trade name "Lerica") for the treatment of diabetic peripheral neuralgia (DPN) and postherpetic neuralgia (PHN). The most common form of neuropathic pain. [0003] There are many synthetic routes for pregabalin, which can be mainly divided into three categories: [0004] (1)Chemical separation method: [0005] The chemi...

AI Technical Summary

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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