Substituted 3-phenoxy- and 3-phenylalkyloxy-2-phenyl-propylamines

#The present patent application relates to new substituted 3-phenoxy- or 3-phenylalkyloxy-2-phenyl-propylamines of general formula 1, processes for preparing them and their use as pharmaceutical compositions.

#wherein

#R1 and R2 independently of one another may denote hydrogen, C1-C8-alkyl, benzyl, furylmethyl, cycloalkyl, cycloalkyl-methyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkoxy-(CH2)1—, C3-C8-cycloalkoxy-(CH2)m— and

#126 g (0.87 mol) of 2,6-dimethylphenylacetonitrile are dissolved in 450 ml toluene and combined with 450 ml of ethyl formate. The mixture is cooled to a temperature of −10° C. and 144 g (1.29 mol) of potassium-tert.-butoxide are added in batches, so that the temperature does not exceed −5° C. It is left to react for a period of 30 minutes (min) at −5° C. and then for 2 hours (h) at ambient temperature. It is then extracted twice with 500 ml of water, the aqueous phase is made acidic with 100 ml of concentrated hydrochloric acid and extracted twice more with 500 ml of methylene chloride (dichloromethane). The organic phase is dried and concentrated by evaporation in vacuo. The residue is recrystallised from petroleum ether. Yield: 139 g (92% of theory).

#58 g (0.33 mol) of hydroxymethylene-2,6-dimethylphenylacetonitrile are dissolved in 250 ml methanol and combined with 37 g (0.59 mol) of sodium cyanoborohydride. After 2 h, 250 ml of acetic acid are added dropwise, during which time the mixture heats up to 50° C. After the exothermic reaction has died down, the mixture is refluxed for a further 3 h. It is left to cool and the mixture is evaporated down in vacuo. The residue is mixed with 500 g of ice, neutralised with ammonia and extracted twice with 500 ml of ethyl acetate. The combined organic extracts are washed with 100 ml of water. After drying, the solvent is eliminated in vacuo. The residue is further processed from the crude state. 54.1 g (92% of theory) of the title compounds are obtained in the form of an oil.

#52.4 g (0.3 mol) of 3-hydroxy-2-(2,6-dimethylphenyl)-propionitrile are dissolved in 400 ml methanol and combined with 50 9 of NH3. The reaction mixture is hydrogenated under a pressure of 70 bar and at a reaction temperature of 70° C. in the presence of 60 g Raney nickel. After 4 h the mixture is cooled, filtered over silica gel and the solvent is eliminated in vacuo. The residue is distilled under high vacuum. Yield: 40.6 g (76%), boiling point: 135-140° C. (0.02 mbar); melting point of the hydrochloride: 166° C.