A PROCESS FOR THE PREPARATION OF ISOMERS OF 11-3-(DIMETHYLAMINO)PROPYLIDENE-6, 11-DIHYDRODIBENZ b, e OXEPIN-2-ACETIC ACID HYDROCHLORIDE AND POLYMORPHS THEREOF

摘要

The present invention relates to an improved process for the preparation of 1 1 -(Z)-[3- (Dimethylamino) propyl idene] -6, 1 l-dihydrodibenz[b,e]oxepin-2-acetic acid (Olopatadine hydrochloride) by reaction of l l-oxo-6, l l -dihydrodibenz[b,e] oxepin-2-acetic acid with Grignard reagent of l-halo-3-dimethylaminopropane and further dehydrated with or without isolation of the intermediate 1 l -(3-dimethylaminopropyl)-l l -hydroxy-6,l l- dihydrodibenz[b,e]oxepin-2-acetic acid. The present invention relates novel polymorphs of 1 1 -(Z)-[3-(Dimethylamino) propyl idene] -6, 1 l -dihydrodibenz[b,e]oxepin-2-acetic acid (Olopatadine hydrochloride). The present invention further relates to preparation of 1 1 - (E)-[3-(Dimethylamino) propylidene]-6, l l-dihydrodibenz[b,e]oxepin-2 -acetic acid hydrochloride.