Process for preparing intermediates of peripherally-selective inhibitors of dopamine-β-hydroxylase involving catalytic asymmetric hydrogenation

Abstract

A process for preparing the S or R enantiomer of a compound of formula A, the process comprising subjecting a compound of formula B to asymmetric hydrogenation in the presence of a chiral transition metal catalyst and a source of hydrogen, wherein X is CH, oxygen, or sulphur; R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino, or dialkylamino group; and Ris alkyl or aryl, wherein the transition metal catalyst comprises a chiral ligand having the formula wherein p is from 1 to 6, and Ar means aryl group; wherein the term alkyl means hydrocarbon chains, straight or branched, containing from one to six carbon atoms, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups; the term aryl means an aromatic or heteroaromatic group, optionally substituted by alkyloxy, halogen, or nitro group; and the term halogen means fluorine, chlorine, bromine, or iodine.