R-4- E-2- AN IMPROVED PROCESS FOR THE PREPARATION OF R-4-PROPYL PYRROLIDINE-2-ONE A KEY INTERMEDIATE FOR SYNTHESIS OF BRIVARACETAM

R-4- E-2- AN IMPROVED PROCESS FOR THE PREPARATION OF R-4-PROPYL PYRROLIDINE-2-ONE A KEY INTERMEDIATE FOR SYNTHESIS OF BRIVARACETAM

A process for the preparation of (R)-4-propyl-pyrrolidin-2-one comprises: a step of selectively enzymatically converting dimethyl 3-propyl pentanedioate to (S)-3-(2-methoxy-2-oxoethyl)hexanoic acid using Novozyme's Promea® enzyme, obtaining (S)-3-(2-amino-2-oxoethyl)hexanoic acid having a high...

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Bibliographische Detailangaben
Hauptverfasser: MURALI KRISHNA PRASAD DIVI, NAGESWARA RAO BOLNENI, LEELA MAHESWARA RAO BANDARUPALLI
Format: Patent
Sprache:eng ; kor
Schlagworte:
BEER
BIOCHEMISTRY
CHEMISTRY
COMPOSITIONS THEREOF
CULTURE MEDIA
ENZYMOLOGY
FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE
METALLURGY
MICROBIOLOGY
MICROORGANISMS OR ENZYMES
MUTATION OR GENETIC ENGINEERING
PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS
SPIRITS
VINEGAR
WINE
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Zusammenfassung:A process for the preparation of (R)-4-propyl-pyrrolidin-2-one comprises: a step of selectively enzymatically converting dimethyl 3-propyl pentanedioate to (S)-3-(2-methoxy-2-oxoethyl)hexanoic acid using Novozyme's Promea® enzyme, obtaining (S)-3-(2-amino-2-oxoethyl)hexanoic acid having a high calyral purity of more than 99% through amidation of the (S)-3-(2-methoxy-2-oxoethyl)hexanoic acid followed by ester hydrolysis, converting the amide into an amine through Hoffmann rearrangement, and obtaining (R)-4-propyl-pyrrolidin-2-one through cyclization. This is further converted to brivaracetam by N-alkylation using 2-bromobutyric acid, followed by enzymatic separation after esterification. (R)-4-프로필-피롤리딘-2-온의 제조를 위한 공정은 Novozyme의 Promea® 엔자임을 이용한 디메틸 3-프로필 펜탄디오에이트를 선택적으로 (S)-3-(2-메톡시-2-옥소에틸) 헥산산으로 엔자임적으로 전환하고, (S)-3-(2-메톡시-2-옥소에틸)헥산산의 아미드화, 이어서 에스테를 가수분해를 통하여 99% 초과의 고 카리랄 순도를 갖는 (S)-3-(2-아미노-2-옥소에틸)헥산산을 얻고, 아미드를 호프만 재배열에 의하여 아민으로 전환하고, 고리화를 하여 (R)-4-프로필-피롤리딘-2-온을 얻는 단계를 포함한다. 이는 나아가 2-브로모부틸산을 이용한 N-알킬레이션에 의하여 브리바라세탐으로 전환되고, 에스테르화 이후 엔자임적 분리가 수행된다.