	US 12,227,476 B2
	Preparation method for levetiracetam intermediate
Bingxin Liu, Zhejiang (CN); Yulong Gong, Zhejiang (CN); Yuanxun Zhu, Zhejiang (CN); and Fengfeng Yan, Zhejiang (CN)
Assigned to ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD., Zhejiang (CN)
Appl. No. 17/600,535
Filed by ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD., Zhejiang (CN); ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL CO., LTD., Zhejiang (CN); and ZHEJIANG HUAHAI TIANCHENG PHARMACEUTICAL CO., LTD, Zhejiang (CN)
PCT Filed Apr. 17, 2020, PCT No. PCT/CN2020/085370 § 371(c)(1), (2) Date Sep. 30, 2021, PCT Pub. No. WO2020/216146, PCT Pub. Date Oct. 29, 2020.
Claims priority of application No. 201910328462.9 (CN), filed on Apr. 23, 2019.
Prior Publication US 2022/0162165 A1, May 26, 2022
Int. Cl. C07D 207/27 (2006.01)

CPC C07D 207/27 (2013.01)

6 Claims

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.