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Method for preparing high-purity gabapentin

A technology of gabapentin and acid hydrolysis is applied in the field of preparation of high-purity gabapentin, which can solve the problems of affecting the purity of finished products, large amount of strong base and high impurity content, and achieve the effects of improving purity and yield, improving total yield and high purity

Active Publication Date: 2014-02-12
浙江精进药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Excessive temperature in the reaction process will cause high impurity content, which will eventually affect the purity of the finished product; the molar ratio of 2-aza-spiro[4,5]-3-decanone to strong acid is 2-15:1 to prepare gabapentin salt salt, the mother liquor of acidolysis is neutralized with lye, and 2-aza-spiro[4,5]-3-decanone is recovered by reflux under alkaline conditions, and the amount of strong acid and strong base is relatively large; the crude product prepared from gabapentin hydrochloride has no In the process of organic solvent purification, the purity is not high enough; 2-aza-spiro[4,5]-3-decanone prepares the total yield of gabapentin fine product as 73.4% (relative to 2-aza-spiro[4,5] -3-decanone), the purity is 99.8% (HPLC), and the yield and the purity all need to be further improved.

Method used

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  • Method for preparing high-purity gabapentin

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Effect test

Embodiment 1

[0053] Embodiment 1: a kind of preparation method of high-purity gabapentin, carries out following steps successively:

[0054] 1), the preparation of gabapentin hydrochloride:

[0055] In a 500ml autoclave, add 2-aza-spiro[4,5]-3-decanone 40g, water 40g, refined hydrochloric acid 100g (refined hydrochloric acid is the hydrochloric acid aqueous solution that mass concentration is 36%), seals reaction system, adds Press down to 0.8MPa, heat up to reflux. After reacting for 3 hours, it was slowly lowered to room temperature (cooling treatment with tap water), and the ice-water bath continued to cool down to 0-4 ° C, stirred at 0-4 ° C for 3 h, and filtered with suction to obtain 59.9 g of gabapentin hydrochloride wet product (measured moisture content 211 %, yield 87.2%), 45 ℃ oven dry weight 49.8g, purity 98.4% (HPLC); Obtain acidolysis mother liquor 109.0g, this acidolysis mother liquor is through titration (i.e. adopt titration method to measure the mass content of hydrochlo...

Embodiment 2

[0076] Embodiment 2, a kind of preparation method of high-purity gabapentin, carries out following steps successively:

[0077] 1), the preparation of gabapentin hydrochloride

[0078] Add 40 g of 2-aza-spiro[4,5]-3-decanone and 140 g of refined hydrochloric acid into a 500 ml autoclave, close the reaction system, pressurize to 0.5 MPa, and raise the temperature to reflux. After reacting for 4 hours, it was slowly lowered to room temperature, continued to cool down to 0-4°C in an ice-water bath, stirred at 0-4°C for 3 hours, and filtered with suction to obtain 55.8 g of gabapentin hydrochloride wet product (moisture content: 19.1%, yield: 83.3%) , dried at 45°C, weighing 47.8g, purity 98.0% (HPLC); 117.1g of acidolysis mother liquor was obtained, and the titration content of hydrochloric acid in the acidolysis mother liquor was 33.5%.

[0079] 2), the application of acidolysis mother liquor (1):

[0080] Add 40g of 2-aza-spiro[4,5]-3-decanone to a 500ml autoclave, 117.1g of ...

Embodiment 3

[0093] Embodiment 3, a kind of preparation method of high-purity gabapentin, the pressure in step 1), step 2) and step 3) is changed into 1.5MPa; All the other are the same as embodiment 1.

[0094] Use 2-aza-spiro[4,5]-3-decanone 120g in total, refined hydrochloric acid 165.2g, can get gabapentin crude product 127.8g (measure moisture content 9.3%), finally get gabapentin fine product 105.0g (total yield 78.3%) %, purity 99.9%), individual impurity is less than 0.05%.

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Abstract

The invention discloses a method for preparing high-purity gabapentin, which comprises the following steps: 1) subjecting 2-aza-spiro[4,5]-3-decanone to reflux acidolysis in strong acid or aqueous solution of strong acid under pressure and obtaining gabapentin strong acid salt and acidolysis mother solution; 2) recycling the obtained acidolysis mother solution for preparing gabapentin strong acid salt; 3) repeating the step 2); 4) obtaining gabapentin strong acid salt obtained by the two steps and preparing coarse gabapentin; and 5) dissolving the coarse gabapentin in aqueous solution of lower alcohol, distilling under reduced pressure and recrystallizing. The high-purity gabapentin can be obtained by using the method, and the method has the characteristics of high yield, low cost and the like.

Description

technical field [0001] The invention relates to a process for preparing high-purity gabapentin, that is, a process for preparing 1-(methylamino)cyclohexaneacetic acid, which belongs to the technical field of medicine preparation. Background technique [0002] Gabapentin (Gabapentin), trade name Neurotin, chemical name 1-(methylamino)cyclohexaneacetic acid, its molecular structure is similar to γ-aminobutyric acid (GABA), was first successfully developed by the Warner-Lambert Company of the United States, and was first released in 1993 It was launched in the UK as an adjuvant anti-epileptic drug, and was approved by the US Food and Drug Administration (FDA) for listing in the US the following year. Later, in clinical research, it was found that gabapentin also has a significant effect on various chronic pains, and at the same time, it has no hepatic metabolism, small adverse reactions, and good compliance. In 2002, it was approved by the FDA for the treatment of neuropathic p...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C229/28C07C227/22
Inventor 赵金浩杜冲李斌陈文旭王晖
Owner 浙江精进药业有限公司
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