Patent ID: 8093391
Filing Date: 2012-01-10
Classification: C07D

Abstract:
1. An improved and scalable process for the preparation of palonosetron and its acid addition salts, in particular hydrochloride (I) represented by the following structure with NMT (not more than) 0.40% of the undesired (3aR,S) isomer; which comprises of, (a) converting intermediate (IIa) as such or as its freebase (II) to a crude mixture of diastereomeric palonosetrons (VIII) or (VIIIa) contaminated with varying amounts of unconverted intermediate (II) or (IIa) via hydrogenation under pressure with an appropriately chosen hydrogenation catalyst in an suitable organic solvent; (b) treating the obtained crude diastereomeric palonosetrons (VIII) or hydrochloride (VIIIa) with a halogenating reagent chosen from bromine, chlorine, iodine, N-bromosuccinimide, N-chlorosuccinimide, N-iodosuccinimide, bromine-triphenylphosphine, chlorine-triphenylphosphine, N-bromophthalamide, N-chlorophthalimide in the presence or absence of free radical initiator to remove the unreduced intermediate II or IIa; and (c) finally, converting the resulting diastereomeric palonosetron (VIII) or its hydrochloride (VIIIa) to the desired palonosetron hydrochloride (I) via selective crystallization from a suitable single or mixture of organic solvents.