HYDROGENATION OF A CHIRAL 1H-BENZ[DE]ISOQUINOLIN-1-ONE AND AN EQUILIBRATION USING PALLADIUM CATALYST

The catalytic hydrogenation of a chiral 1H-benz[de]isoquinolin-1-one t o palonosetron and the undesired diastereomer was optimized using a va riety of conditions and catalysts, The most selective catalyst for the production of palonosetron was an unreduced palladium on carbon catal yst. The(+)- and (-)-camphorsulfonic acid salts of the 1H-benz[de]isoq uinolin-1-one and the complex of the 1H-benz[de]isoquinolin-1-one with Mg2+ upon catalytic hydrogenation gave the greatest preference for th e undesired diastereomer, An equilibration of the undesired diastereom er from hydrogenation and palonosetron as hydrochloride salts using hy drogen-activated palladium on carbon catalyst under a nitrogen atmosph ere was developed, The procedure was used to recycle the hydrochloride salt of the undesired diastereomer from hydrogenation into pure palon osetron hydrochloride.