Preparation method for levetiracetam intermediate

Patent metadata

Field	Value
Publication number	US-12227476-B2
Application number	US-202017600535-A
Country	US
Kind code	B2
Filing date	Apr 17, 2020
Priority date	Apr 23, 2019
Publication date	Feb 18, 2025
Grant date	Feb 18, 2025

Abstract

A high-quality (RS)-α-ethyl-2-oxo-1-pyrrolidine acetic acid acquired by racemization recovery is provided. A method provided significantly increases the quality and appearance of the product (RS)-α-ethyl-2-oxo-1-pyrrolidine acetic acid recovered using racemization and does not affect the product yield.

First claim

The invention claimed is:

1. A method for preparing (RS)-α-ethyl-2-oxo-1-pyrrolidineacetic acid, comprising the following steps:
(a) adding a mixture comprising (R)-α-ethyl-2-oxo-1-pyrrolidineacetic acid and (S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid to a strong base aqueous solution, heating to 80-95° C. and stirring at this temperature for 8-12 hours;
(b) adding an appropriate amount of water for dilution, cooling to 40-60° C. and adjusting to pH=6.0-8.0 by adding hydrochloric acid dropwise;
(c) adding activated carbon or diatomite for adsorption and decolorization while keeping a temperature of 40-60° C., and then filtering while hot to obtain a filtrate;
(d) heating the filtrate and controlling the temperature in the range of 70-90° C., and adjusting to pH=1.0-2.5 by adding hydrochloric acid dropwise; and
(e) cooling to 0-10° C., filtering and drying to obtain (RS)-α-ethyl-2-oxo-1-pyrrolidineacetic acid.

2. The method according to claim 1 , wherein the strong base in step (a) is sodium hydroxide or potassium hydroxide.

3. The method according to claim 1 , wherein a mass percentage concentration of the strong base aqueous solution in step (a) is in the range of 25% to 40%.

4. The method according to claim 1 , wherein the amount of the strong base in step (a) is 1-3 times of a total molar quantity of the mixture comprising (R)-α-ethyl-2-oxo-1-pyrrolidineacetic acid and (S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid.

5. The method according to claim 1 , wherein the amount of water in step (b) is 1.5-5 times of the total mass of the mixture comprising (R)-α-ethyl-2-oxo-1-pyrrolidineacetic acid and (S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid.

6. The method according to claim 1 , wherein the time of the decolorization in step (c) is 0.5 to 1.5 hours.

Assignees

• Zhejiang Huahai Pharm Co Ltd
• Zhejiang Huahai Zhicheng Pharmaceutical Co Ltd
• Zhejiang Huahai Tiancheng Pharmaceutical Co Ltd

Inventors

• Liu Bingxin
• Gong Yulong
• Zhu Yuanxun
• Yan Fengfeng

Classifications

• C07B2200/07

  Optical isomers · CPC title

• C07D207/27 Primary

  with substituted hydrocarbon radicals directly attached to the ring nitrogen atom · CPC title