New catalytic route for the synthesis of an optically active tetralone-derived amine for rotigotine

Rotigotine is a launched drug for the treatment of Parkinson's disease and restless legs syndrome. The key steps of an alternative route for the synthesis of rotigotine have been demonstrated. Formation of a prochiral enamide, asymmetric hydrogenation of the enamide with high enantioselectivity, and reduction of the resulting amide to an amine have been proved to work successfully. The best conditions screened to date for the asymmetric hydrogenation of enamide 9 to amide 10 were with [(RuCK(R)-T-BINAP))(2)(mu-Cl)(3)][NH2Me2] at 25 bar H-2 and 30 degrees C (500:1 S/C ratio, 99% conversion, 91% ee S). Reduction of amide 10 to amine 5 was best achieved with Red-Al giving 95% conversion. (C) 2016 Elsevier Ltd. All rights reserved.