63095-51-2Relevant articles and documents
COMPOUND AND USE THEREOF IN SYNTHESIS OF BRIVARACETAM INTERMEDIATE AND CRUDE DRUG
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Page/Page column 0096-0100, (2021/08/27)
The present application provides a compound in formula III, and further provides a use of the compound in the synthesis of a Brivaracetam intermediate and a crude drug, and a synthesis method. A raw material involved in the method of the present application is low in costs and easily available; (R)-4-propyl-dihydrofuran-2-ketone having high optical purity can be prepared; complicated separation and purification steps are avoided; costs are reduced, and the method is more applicable to industrial production.
Preparation method of brivaracetam intermediate
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Paragraph 0025; 0070-0071, (2021/09/04)
The invention provides a preparation method of a brivaracetam intermediate (R)-3-propyl-gamma-butyrolactone, which comprises the following steps: by taking 4-chloro-4-oxobutyric acid methyl ester as a starting raw material, connecting a chiral auxiliary group, introducing R configuration propyl, removing a ligand, reducing carboxyl, and finally esterifying to form a ring, thereby obtaining the (R)-3-propyl-gamma-butyrolactone. The synthesis route ingeniously utilizes the chiral adjuvant (R)-4-benzyl-2-oxazolidinone, optimizes the reaction conditions, has the advantages of few reaction steps, high yield, good reaction stereoselectivity and the like, meanwhile, the raw materials are cheap and easy to obtain, the operation is simple, convenient and safe, and the method has a better industrial application prospect;.
Identification, characterization, synthesis and strategy for minimization of potential impurities observed in the synthesis of brivaracetam
Liao, Shouzhu,Chen, Hongjun,Wang, Guifei,Wu, Shuming,Yang, Zaiyou,Luo, Weihe,Liu, Zhuanfeng,Gao, Xun,Qin, Junhai,Li, Chuan-hua,Wang, Zhongqing
, (2020/05/25)
A first systematic impurity profile research concerning nine observed and potential process related impurities of antiepileptic drug brivaracetam is reported. Among which three (impurity G/H/I) have not been discovered or reported before, these nine impurities were monitored by HPLC, and their structures were identified on the basis of MS and NMR spectroscopy. In addition to the formation, synthesis, and characterization, strategies for minimizing these impurities to the levels accepted by ICH are also described in this report.