A PROCESS FOR THE PREPARATION OF 2-[N-­ [(S)-1-ETHOXYCARBONYL-3-PHENYLPROPYL]-(S)-ALANYL]-(1S, 3S, 5S) -2-AZABICYCLO [3.3.0] OCTANE-3­-CARBOXYLIC ACID

A PROCESS FOR THE PREPARATION OF 2-[N-­ [(S)-1-ETHOXYCARBONYL-3-PHENYLPROPYL]-(S)-ALANYL]-(1S, 3S, 5S) -2-AZABICYCLO [3.3.0] OCTANE-3­-CARBOXYLIC ACID

A process for preparation of 2-[N-[(S)-l­-ethoxycarbonyl-3-phenylpropyl] - (S) -alanyl]-(1S, 3S, 5S)-2­- azabicyclo [3.3.0 ] octane-3-carboxylic acid, ie. Ramipril, involves condensation of an activated derivative of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine with racemic (1R, 3R, 5R) -2...

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Bibliographische Detailangaben
Hauptverfasser: WACHAL, TERESA, BANKOWSKI, KRZYSZTOF, SIDORYK, KATARZYNA, SZELEJEWSKI, WIESLAW
Format: Patent
Sprache:eng ; fre
Schlagworte:
CHEMISTRY
HETEROCYCLIC COMPOUNDS
METALLURGY
ORGANIC CHEMISTRY
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Zusammenfassung:A process for preparation of 2-[N-[(S)-l­-ethoxycarbonyl-3-phenylpropyl] - (S) -alanyl]-(1S, 3S, 5S)-2­- azabicyclo [3.3.0 ] octane-3-carboxylic acid, ie. Ramipril, involves condensation of an activated derivative of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine with racemic (1R, 3R, 5R) -2-azabicyclo [3.3.0] octane-3­-carboxylic acid, and then the desired diastereoisomer (la) is separated from the obtained diastereoisomeric mixture of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]­(S) -alanyl] - (1S, 3S, 5S) -2-azabicyclo [3.3.0] octane-3-­carboxylic acid (1a) and 2- [N-[(S)-1-ethoxycarbonyl-3-­phenylpropyl ] - (S) -alanyl ] - (1R, 3R, 5R) -2- azabicyclo[3.3.0]octane-3-carboxyl ic acid (lb) by treat­ing it with a solvent that selectively dissolves the un­desired diastereoisomer (1b) while the diastereoisomer (1a) remains undissolved. L'invention concerne un procédé de préparation d'acide 2-[N-[(S)-1-éthoxycarbonyl-3-phénylpropyl]-(S)-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylique,à savoir, le ramiprile. Ce procédé consiste d'abord à soumettre un dérivé activé de 2-[N-[(S)-1-éthoxycarbonyl-3-phénylpropyl]-(S)-alanine à la condensation avec l'acide racémique (1R, 3R, 5R)-2-azabicyclo[3.3.0] octane-3-carboxyliqe, et à séparer ensuite le diastereoisomère souhaité (1a) du mélange diastereoisomérique obtenu d'acide 2-[N-[(S)-1-éthoxycarbonyl-3-phénylpropyl]-(S)-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0] octane-3-carboxylique (1a) et l'acide 2-[N-[(S)-1-éthoxycarbonyl-3-phénylpropyl]-(S)-alanyl]-(1R, 3R, 5R)-2-azabicyclo[3.3.0]octane-3-carboxylique (1b) par traitement avec un solvant qui dissout sélectivement le diastereoisomère (1b) non voulu, et maintient le diastereoisomère (1a) non dissous.