Hydrogenation of a Chiral 1H-Benz[de]isoquinolin-1-one and an Equilibration Using Palladium Catalyst

Abstract

The catalytic hydrogenation of a chiral 1H-benz[de]isoquinolin-1-one to palonosetron and the undesired diastereomer was optimized using a variety of conditions and catalysts. The most selective catalyst for the production of palonosetron was an unreduced palladium on carbon catalyst. The (+)- and (−)-camphorsulfonic acid salts of the 1H-benz[de]isoquinolin-1-one and the complex of the 1H-benz[de]isoquinolin-1-one with Mg2+ upon catalytic hydrogenation gave the greatest preference for the undesired diastereomer. An equilibration of the undesired diastereomer from hydrogenation and palonosetron as hydrochloride salts using hydrogen-activated palladium on carbon catalyst under a nitrogen atmosphere was developed. The procedure was used to recycle the hydrochloride salt of the undesired diastereomer from hydrogenation into pure palonosetron hydrochloride.