Hydrochloric Acid → Palonosetron hydrochloride

Participants

Reaction Conditions

Reaction Steps

The diastereomeric palonosetron (VIII) (5.0 g) showing 54.06% of the desired (S, S) isomer, 42.13% of the undesired (3aR, S) isomer (Ia) and 1.04% of unreacted compound (IIa) 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 neat liquid bromine (100 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 2.2 g of the precipitated crude palonosetron hydrochloride (I) was isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 96.41% of the desired (3aS, S) isomer, 3.59% of the undesired (3aR, S) isomer (Ia) and no unreacted compound (IIa) on HPLC, was then crystallized twice from ethanol-methanol mixture to give 1.5 g of the title product (I) which was found to contain 99.62% of the titled compound (I) and 0.38% (3aR, S) isomer (Ia) while no unreacted intermediate (IIa) could be detected by HPLC analysis.

Provenance & Evidence