Preparation of levo-salbutamol, useful as bronchodilator, by asymmetrical catalytic hydrogenation of its ketone precursor in presence of rhodium and chiral phosphine

摘要

Method for producing levo-salbutamol (I; alpha-(((1,1-dimethylethyl)amino)methyl)-4-hydroxy-1,3-benzenedimethanol) or its salts by asymmetric hydrogenation of prochiral salbutamone (II) in presence of rhodium and a chiral, bidentate phosphine ligand (III), optionally followed by treatment with acid to form a salt. An Independent claim is also included for preparation of (I) by: (1) bromination of 4-acetoxy-3-acetoxymethylacetophenone; (2) reaction of the product with N-tert-butyl-N-benzylamine; (3) hydrogenation of palladium catalyst (debenzylation); (4) hydrogenation of the resulting (II) by the new method and (5) optionally treatment with acid.