Hydrochloric Acid → Palonosetron hydrochloride

Participants

Reaction Conditions

Reaction Steps

The diastereomeric palonosetron (VIII) (10.0 g) as obtained above was dissolved in 42.0 ml of 5% methanol in ethanol (4.2 volumes). To it hydrochloric acid in ethanol was added and was heated to 70-75° C. Then N-bromosuccinimide (200 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 5.5 g of the precipitated crude palonosetron hydrochloride (I) was isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 94.65% of the desired (3aS, S) isomer, 4.14% of the undesired (3aR, S) isomer (Ia) and 0.30% of unreacted compound (VI), when crystallized twice from ethanol-methanol mixture containing 20 mg of N-bromosuccinimide yielded 2.0 g of the title product (I) which was found to contain 99.60% of the titled compound (I), 0.40% (3aR, S) isomer (Ia) and intermediate (IIa) below detection limit by HPLC analysis.

Provenance & Evidence