Synthesis method of gabapentin hydrochloride

Abstract

The invention relates to a synthesis method of gabapentin hydrochloride. The method comprises the following steps of: with 1,1-cyclohexyldiacid monoacyl amine as a starting material, carrying out a Hoffman degradation reaction; dewatering and condensing; carrying out product phase transfer; and hydrolyzing. The method artfully integrates relevant processes in the prior art and realizes the preparation of the gabapentin hydrochloride through the generation and the phase transfer of 3,3-pentylidene butyrolactam in a reaction process; the reaction does not relate to an acidification process, avoids the consumption of a large quantity of inorganic acids and the generation of inorganic salts and thoroughly solves the problem of difficult separation of the gabapentin hydrochloride in the original process; and in the reaction process, an organic solvent is directly cycled and mechanically applied and closed in the reaction process all the time, which is hopeful to realize the zero organic solvent discharge of the process. The method has the advantages of reasonable process design, simpleness and convenience of operation, high raw material conversion rate and high yield.

Description

The synthetic method of gabapentin hydrochloride technical field The invention relates to a synthesis process of gabapentin hydrochloride, which belongs to the field of chemical synthesis. technical background The chemical name of Gabapentin (Gabapentin) is 1-(aminomethyl)-cyclohexylacetic acid, and its structure is similar to GABA. It can be used for the treatment of certain forms of epilepsy and hypokinesia. U.S. Patents US4024175 and US4087544 cover this compound and its use. Recent clinical applications have shown that the drug is effective in the treatment of various pains, especially in intractable neuropathic pain and postoperative pain. Due to less adverse reactions and no interaction with other drugs, this drug may become a promising analgesic or analgesic adjuvant drug. As the precursor of gabapentin, gabapentin hydrochloride is called 1-(aminomethyl)-cyclohexylacetic acid hydrochloride. Pentylglutarimide is used as a raw material, which is obtained through L...

AI Technical Summary

Problems solved by technology

Among them, the existing patent situation of the second process route: using 1,1-cyclohexyloxalic acid monoamide as the starting material, through the Hofmann degradation reaction, the reaction solution is directly acidified to prepare gabapentin hydrochloride, and its disadvantage lies in the acidification To consume a large amount of inorganic acid, a large amount of inorganic salts and acidic organic impurities are generated at the same time, and it is difficult to separate the product gabapentin hydrochloride from the reaction solution, no matter the organic solvent extraction currently used, or concentration first and then extraction, or liquid-liquid extraction (US20080207945), its operation is all more loaded down with trivial details, it is difficult to realize continuous production