Palonosetron salts and processes for preparation and purification thereof
View Patent ↗Provided are novel salts of 2-(1-azabicyclo-[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one, methods of using such salts, and processes for producing such salts.
1. A method of purifying a palonosetron hydrobromide salt comprising:
(a) dissolving or partially dissolving an impure (3S),(3aS) palonosetron hydrobromide salt in at least one organic solvent;
(b) optionally heating the solution or partial solution of step (a) to a temperature greater than 30° C.; and
(c) cooling the solution or partial solution of step (a) or step (b) to a temperature below 20° C. for a time sufficient to permit crystallization of the pure salt of (3S),(3aS) palonosetron, wherein the impure salt of (3S),(3aS) isomer has a purity of up to 99.1% and an isomer ratio of (3S),(3aS) isomer:(3S),(3aR) isomer of up to 97:3, and the pure salt of palonosetron has a purity of at least 99.5% and an isomer ratio of 99:1 or greater.
2. The method of claim 1 , further comprising collecting the crystals of the pure palonosetron.
3. The method of claim 2 , wherein the collection is via filtration.
4. The method of claim 1 , wherein the at least one organic solvent is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, dichloromethane, chloroform, n-pentane, n-hexane, cyclohexane, n-heptane, petroleum ether, and mixtures thereof.
5. The method of claim 4 , wherein the at least one organic solvent is ethanol or a 1:1:1 mixture (by volume) of methanol: dichloromethane: petroleum ether.