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

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 catalyst and a source of hydrogen,
• wherein X is CH2, oxygen or sulphur;
• R1, R2 and R3 are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group;
• and R4 is alkyl or aryl, 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 a phenyl or naphthyl group, optionally substituted by alkyloxy, halogen or nitro group;
• and the term halogen means fluorine, chlorine, bromine, or iodine, wherein the chiral catalyst comprises a ligand which is the S or R enantiomer of TolBINAP and the reaction is carried out at a temperature from above 70° C. to 100° C. and in the presence of an acid at a concentration of 0.05 to 0.2%.