Preparation of gabapendin

A technology of gabapentin and gabapentin salt, which is applied in the field of preparation of gabapentin, can solve the problems of high equipment requirements, high energy consumption, difficult content control, and complicated process, and achieve the effects of easy operation, low energy consumption, and simple process

Active Publication Date: 2008-07-02
ZHEJIANG CHIRAL MEDICINE CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The invention provides a preparation method of pharmaceutical grade gabapentin which is simple, practical, high in yield and easy for industrialized production, which solves the complex process, long production cycle, high equipment requirements and energy consumption in the prior art, and the use of alcohol It is difficult to control the content of toxic impurities 3,3-pentylidenebutyrolactam and chloride ions in the finished product, low yield and high cost, etc.

Method used

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  • Preparation of gabapendin
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  • Preparation of gabapendin

Examples

Experimental program
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Effect test

Embodiment 1

[0042] Embodiment 1 Preparation of gabapentin hydrochloride

[0043] In a 2000ml reaction flask, add 167g of 3,3-pentamethylenebutyrolactam, 900g of 31% concentrated hydrochloric acid and 200ml of purified water, stir, heat up and reflux for 5 hours, and cool the reaction solution to -5~5 ℃, filtered to obtain the wet product of white crystal gabapentin hydrochloride, which is equivalent to 206.5 grams of dry product (water of crystallization is measured and deducted by the Karl-Fisher method), yield 91.1%, purity 98.5%, 3,3-pentamethylene butyl Lactam content 0.8%. The concentration of the mother liquor hydrochloric acid aqueous solution is about 15% to 18%. A part of the mother liquor (A) is supplemented with 36% concentrated hydrochloric acid for use in the next batch, and the remaining mother liquor (B) is used to recover 3,3-pentylidenebutyrolactam.

Embodiment 2

[0044] Embodiment 2 Preparation of gabapentin hydrochloride

[0045] In a 2000 ml reaction flask, add 167 grams of 3,3-pentylidene butyrolactam, 900 grams of the mother liquor (A) containing hydrochloric acid in Example 1, and add 300 grams of 36% concentrated hydrochloric acid. Stirring, heating and reflux reaction for 5 hours, the reaction solution was cooled to -5~5°C, filtered to obtain the wet product of white crystal gabapentin hydrochloride, which was equivalent to 216 grams of dry product (the water of crystallization was measured and deducted by the Karl-Fisher method), and the The yield is 95.3%, the purity is 98.6%, and the impurity 3,3-pentylidenebutyrolactam content is 0.75%.

Embodiment 3

[0046] The preparation of embodiment 3 gabapentin hydrate

[0047] In a 2000 ml reaction bottle, add 300 ml of purified water, the wet product gabapentin hydrochloride (equivalent to 206 grams of dry product) of Example 1, stir evenly, add 30% sodium hydroxide dropwise at 15~25 ° C, adjust pH =4~6, dissolve, add 1.5g of activated carbon and 0.5g of diatomaceous earth, stir for 0.5 hours, filter, adjust the pH of the filtrate to 8.0~8.5 with 30% sodium hydroxide aqueous solution at 0~10°C, white crystals precipitate, continue to cool to 0-5°C, filter, and wash with a small amount of ice water to obtain the wet product of gabapentin hydrate, which is equivalent to 160 grams of dry product, with a yield of 85.2%, a purity of 99.5%, and an impurity 3,3-pentylidene butyrolactam content <0.1 %. The separated mother liquor (C) is used to recover 3,3-pentylidenebutyrolactam.

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Abstract

Production of gabapentin is carried out by 3,3-pentylidene butyrolactam as initial raw material, hydrolyzing to obtain gabapentin salt, converting it into gabapentin hydrate and elutriating out gabapentin from alcohol solvent, neutralizing while adsorbing and decoluring residual hydrate by active carbon and siliceous earth, controlling pH to 8-8.5 and recovering mother-liquid. It is safe and convenient, has short period, less consumption and higher recovery rate. It can be used for industrial production.

Description

technical field [0001] The invention relates to a preparation method of gabapentin, which uses 3,3-pentylidene butyrolactam as a starting material. Background technique [0002] Gabapentin, chemical name: 1-(aminomethyl)cyclohexylacetic acid, is an antiepileptic drug and is commonly used in the treatment of neuropathic pain and anxiolytic disorders. Satzinger et al. reported it for the first time in US Pat. No. 4,024,175. [0003] There are many literature reports on the preparation methods of gabapentin. The main way is to synthesize gabapentin hydrochloride from different starting materials, remove hydrochloric acid through ion exchange resin or neutralization and precipitation in solution, and obtain gabapentin after post-treatment. [0004] U.S. Patent No. 4,024,175 and U.S. Pat. No. 4,087,544 disclose a preparation method of gabapentin respectively, by 1,1-cyclohexyl monomethyl diacetate and sodium azide in triethylamine acetone solution through Curtius reaction and by...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C227/22C07C229/28
Inventor 刘田春黄有明范伟荣
Owner ZHEJIANG CHIRAL MEDICINE CHEM
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