181289-23-6Relevant articles and documents
Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ-Lactams
Sietmann, Jan,Ong, Mike,Mück-Lichtenfeld, Christian,Daniliuc, Constantin G.,Wiest, Johannes M.
supporting information, p. 9719 - 9723 (2021/03/16)
Asymmetric access to γ-lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)-1-amino-2-indanol for chiral induction. Mechanistic analysis of the key N,O-ketal rearrangement reveals a Curtin–Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ-lactams, including those bearing all-carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further demonstrates the synthetic utility and highlights the general applicability of the presented method.
Method for synthesizing and refining (S)- pregabalin (by machine translation)
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Paragraph 0041-0044; 0050-0053; 0059-0062, (2020/04/17)
The reaction conditions of the method disclosed by the invention are mild, and the method disclosed by the invention is mild in reaction conditions: (S)- kg of crude,methylhexanoic acid is obtained through: degradation, the reaction conditions of the intermediate (R)- (-) - 3 - (isobutyl - 2 2-pyrrolidinone) - 5 - are more moderate, and the reaction conditions of the preparation method, Hoffman are obtained (S)- times by weight, of the preparation method for, pregabalin concentrate (S)- 4 - obtained by hydrolysis-ring; of the raw material, to obtain a high-purity pregabalin intermediate solution (S)- obtained by carrying out hydrolysis (S)- on a crude product with a high purity,methyl.methylhexanoic acid after re-crystallization, to, obtain a high,purity pregabalin product. (by machine translation)
Synthetic method of environment-friendly and efficient pregabalin
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, (2019/02/04)
The invention relates to a synthetic method of environment-friendly and efficient pregabalin. The synthetic method comprises the following steps: 1) dehydrating and condensing acetate and isopentyl aldehyde to obtain 5-methyl-2-hexenoate; 2) performing cyano addition on the 5-methyl-2-hexenoate to obtain (S)-5-methyl-3-cyanohexanoate; 3) performing hydrogen reduction cyclization on the (S)-5-methyl-3-cyanohexanoate to obtain (S)-4-isobutylpyrrolidin-2-one; and 4) performing hydrolysis and ring opening on the (S)-4-isobutylpyrrolidin-2-one to obtain the pregabalin. The synthetic route has the advantages of cheap and easily available raw materials, few reaction steps, mild process conditions, simple operation, high reaction yield and less environment pollution, and is more suitable for industrial production of bulk drug pregabalin.