A method for the preparation of montelukast acid and sodium...

C - Chemistry – Metallurgy – 07 – D

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C07D 215/18 (2006.01)

Patent

CA 2528228

A method for the preparation of montelukast acid sodium salt thereof in amorphous form has been described. The method comprises of following steps: (a) generating the dilithium dianion of 1-(mercaptomethyl)cyclopropane acetic acid, by reacting with alkyl lithium, (b) coupling the said dianion with wet mesylate to get montelukast acid in crude form, (c) obtaining DCHA salt in crude form by adding dicyclohexylamine (DCHA) to crude acid obtained in the above step (b), (d) purifying and converting the said DCHA salt in crude form, to montelukast acid in pure form, and (e) reacting the pure montelukast acid in a polar protic solvent with a source of sodium ion followed by evaporating the solvent and triturating of the residue with non-polar water immiscible solvent.

La présente invention concerne un procédé de préparation d'acide montelukast et de sel de sodium de celui-ci sous forme amorphe. Ce procédé consiste: (a) à générer le dianion de dilithium d'acide 1-(mercaptométhyl)cyclopropane acétique, à le faire réagir avec le lithium alkyle, (b) à coupler ce dianion avec un mesylate humide pour obtenir de l'acide montelukast sous forme brute, (c) à obtenir un sel DCHA sous forme brute par addition de dicyclohexylamine (DCHA) à l'acide montelukast obtenu à l'étape (b), (d) à purifier et à transformer ce sel DCHA sous forme brute en acide montelukast de forme pure et, (e) à faire réagir cet acide montelukast pur dans un solvant protique polaire avec une source d'ion sodium suivi par l'évaporation de ce solvant et à triturer le résidu avec un solvant non polaire non miscible dans l'eau .

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