A short and efficient synthetic route to the 5-HT3 receptor antagonist
s 1 and 2 (palonosetron) was developed. The novel adjustment of the ox
idation states at the necessary centers of imide 7 was accomplished by
hydrogenation, selective sodium borohydride reduction, and dehydratio
n to yield 1. The sodium borohydride reduction of imide 8 was selectiv
e for the C-3 carbonyl versus the C-l carbonyl next to the aromatic ri
ng to give the hydroxy compound 9. It was essential to keep the sodium
borohydride reduction free of oxygen, or diols 10a and 10b were forme
d as significant byproducts.