Process for preparation of chiral amlodipine gentisate

C - Chemistry – Metallurgy – 07 – D

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C07D 211/90 (2006.01) C07D 213/80 (2006.01) C07D 213/803 (2006.01)

Patent

CA 2626438

The present invention relates to a process for the preparation of optically pure amlodipine gentisate, more particularly to a continuous process for the preparation of optically pure amlodipine gentisate with good yield and high optical purity. The processes can be preformed by first reacting racemic (R,S)- amlodipine and optically pure O,O'-dibenzoyltartaric acid in the presence of a solvent including isopropanol to prepare (R)- or (S)- amlodipine dibenzoyltartarate diastereomer or a solvate thereof, treating the prepared amlodipine diastereomeric salt or a solvate thereof with a base and then finally adding gentisic acid.

La présente invention concerne un procédé pour la préparation du gentisate d'amlodipine optiquement pur, plus particulièrement un procédé continu pour la préparation du gentisate d'amlodipine optiquement pur avec un bon rendement et une grande pureté optique. Les procédés peuvent être réalisés par la réaction en premier lieu entre la (R,S)-amlodipine racémique et l~acide O,O~-dibenzoyltartrique optiquement pur en présence d'un solvant comprenant de l'isopropanol pour préparer le diastéréoisomère (R)- ou (S)-dibenzoyltartrate d'amlodipine ou un solvate de celui-ci, puis par le traitement du sel d'amlodipine diastéréoisomère préparé ou d~un solvate de celui-ci avec une base et ensuite finalement par l~addition de l'acide gentisique.

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