PROCEDURE FOR PREPARATION OF N-METHYL-3-(P-TRIFLUOROMETHYLPHENOXY)-3-PHENYL-PROPYLAMINE HYDROCHLORIDE

The submitted invention refers to an improved procedure for preparation of fluoxetine hydrochloride which is used as an antidepressive medicament, i.e. N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine hydrochloride, by a catalytic hydrogenation of 2-benzoyl-N-benzyl-N-methylethylamine base by means of Pt/C or Pd-Pt/C at hydrogen pressure of 5 bar and temperature of 50 degrees Celsius using ethylacetate as solvent where 1-phenyl-3-(N-methyl-amino)-propane-1-ol is produced. This compound is etherified selectively using 1-chloro-4-trifluoromethylbenzene in N-methyl-pyrrolidone at 80 degrees Celsius in presence of KJ and application of potassium-t-butoxide as a base producing N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine, i.e. a fluoxetine base which is transformed in a known way to fluoxetine hydrochloride, i.e. N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine hydrochloride. The yield of fluoxetine hydrochloride amounts to 85-87 % of the theoretical yield. The submitted invention refers to an improved procedure for preparation of fluoxetine hydrochloride which is used as an antidepressive medicament, i.e. N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine hydrochloride, by a catalytic hydrogenation of 2-benzoyl-N-benzyl-N-methylethylamine base by means of Pt/C or Pd-Pt/C at hydrogen pressure of 5 bar and temperature of 50 degrees Celsius using ethylacetate as solvent where 1-phenyl-3-(N-methyl-amino)-propane-1-ol is produced. This compound is etherified selectively using 1-chloro-4-trifluoromethylbenzene in N-methyl-pyrrolidone at 80 degrees Celsius in presence of KJ and application of potassium-t-butoxide as a base producing N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine, i.e. a fluoxetine base which is transformed in a known way to fluoxetine hydrochloride, i.e. N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine hydrochloride. The yield of fluoxetine hydrochloride amounts to 85-87 % of the theoretical yield. Predloženi izum se nanaša na izboljšan postopek za izdelavo fluoksetin hidroklorida, ki se uporablja kot antidepresivno sredstvo, t.j. N-metil-3-(p-triflurometilfenoksi)-3-fenil-propilamin hidroklorida, s katalitskim hidrogeniranjem 2-benzoil-N-benzil-N-metiletilaminske baze s pomočjo Pt/C ali Pd-Pt/C, pri tlaku vodika 5 bar, pri 50 stopinj Celzija z etilacetatom kot topilom, pri čemer nastane 1-fenil-3-(N-metil-amino)-propan-1-ol. To spojino selektivno eterificiramo ob uporabi 1-kloro-4-trifl