Patent ID: 8877974

Claim:
A process for preparing (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol, or an acid addition salt thereof, said process comprising: (a′) reacting a compound corresponding to formula (V): wherein R represents —C 1-6 -alkyl, —C 3-8 -cycloalkyl, —C 1-3 -alkylene-phenyl, —C 1-3 -alkylene-naphthyl, tetrahydropyranyl or —C(═O)—C 1-6 -alkyl, with dimethylamine hydrochloride and paraformaldehyde in an inert reaction medium under Mannich conditions to yield a compound of formula (VI), wherein R has the above defined meaning; and (a″) subsequently resolving the compound of formula (VI), wherein the resolution is carried out by: (i) reacting a compound of formula (VI) with a chiral acid selected from the group consisting of L-(−)-dibenzoyl tartaric acid and L-(−)-dibenzoyl tartaric acid H 2 O to yield a salt, (ii) separating the salt, and (iii) liberating the corresponding compound of formula (I) in the form of a free base, to yield a compound of formula (I) wherein R has the above defined meaning, (a) reacting the compound corresponding to formula (I), with an ethyl magnesium halide in an inert reaction medium under Grignard conditions to yield a compound corresponding to formula (II): wherein R has the above defined meaning, (b) converting the compound of formula (II) to a compound corresponding to formula (III): wherein R has the above defined meaning, optionally in form of an acid addition salt, wherein the conversion is carried out by: (b′) dehydrating the compound of formula (II) to yield a compound corresponding to formula (VII): wherein R has the above defined meaning; and (b″) hydrogenating the compound of formula (VII) using a catalyst in an inert reaction medium in the presence of hydrogen to yield a compound of formula (III), (c) deprotecting the compound of formula (III) to yield (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol corresponding to formula (IV): (d) optionally converting the (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol from (c) into an acid addition salt.