The invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R.sup.2, R.sup.3and R.sup.4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R.sup.1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R.sup.2, R.sup.3, R.sup.4 and Prot are as defined in the specification.