Hydrochloric Acid → Palonosetron hydrochloride

Participants

Reaction Conditions

Reaction Steps

The diastereomeric palonosetron (VIII) (96.0 g) as obtained above was dissolved in 5% methanol in ethanol mixture (4.2 volumes). To it hydrochloric acid in ethanol was added and was heated to 70-75° C. Then N-bromosuccinimide (500 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 53.0 g of the precipitated crude palonosetron hydrochloride (I) were isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 93.74% of the desired (3aS,S) isomer, 6.19% of the undesired (3aR,S) isomer (Ia) and 0.2% of unreacted compound (IIa), when treated again with 200 mg of N-bromosuccinimide in ethanol-methanol mixture yielded 34.0 g of the title product (I) which was found to contain 99.63% of the titled compound (I), 0.32% of the undesired (3aR,S) isomer (Ia) and 0.05% of unreacted intermediate (IIa) by HPLC analysis.

Provenance & Evidence