The present invention relates to a process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by means of homogeneous catalytic hydrogenation of dimethyl-(3-aryl-but-3-enyl)-amines.
Dimethyl-(3-aryl-butyl)-amine compounds have proved to be pharmaceutically active compounds exhibiting excellent analgesic activity and very good tolerability, see EP-A1-0 693 475. WO 2005/000788 A1 describes a process for the preparation of such compounds in which, in a first stage, substituted dimethyl-(3-aryl-but-3-enyl)-amine compounds are prepared by elimination of the tertiary hydroxyl group in substituted 4-dimethylamino-2-aryl-butan-2-ol compounds. These dimethyl-(3-aryl-but-3-enyl)-amine compounds are then hydrogenated in a second stage in the presence of metal catalysts. The heterogeneous hydrogenation proceeds in good yields with adequate activities. As expected, the stereoselectivity is not very pronounced. According to the examples in WO 2005/000788 A1, if two adjacent asymmetric C atoms are present diastereomeric ratios of from 2:1 to a maximum of 3:1 can be obtained for the trans diastereomer: cis diastereomer, that is to say always in favor of the trans diastereomer. The ratio is established automatically, essentially depends on the substrate, and can be influenced by the choice of reaction conditions to only a small extent.