Fluoxetine → 3-(Dimethylamino)-1-phenylpropan-1-ol

Beteiligte Stoffe

Reaktionsschritte

In the process for the preparation of fluoxetine, as in U.S. Pat. No. 4,314,081, β-dimethylaminopropiophenone hydrochloride is used as a starting material which, after the liberation of the base, is hydrogenated with diborane, B2H4. The N,N-dimethyl-3-hydroxy-3-phenylpropylamine produced in the reaction is allowed to react with thionyl chloride in chloroform containing hydrochloric acid yielding N,N-dimethyl-3-phenyl-3-chloropropylamine. This compound is allowed to react under alkaline conditions with p-trifluoro-methylphenol by heating the mixture under reflux for 5 days and nights, after which N,N-dimethyl-3-p-trifluoromethylphenoxy-3-phenylpropylamine is produced. This compound is N-demethylated with the aid of cyanogen bromide, yielding N-methyl-N-cyano-3-(p-trifuoromethylphenoxy)-phenylpropylamine. The N-cyano group is removed from this compound by heating for 20 hours at 130° C. under reflux in a mixture of potassium hydroxide and ethylene glycol. The reaction mixture is extracted with ether and the ether phase is evaporated to dryness. The residue could further be transformed in a known manner into a pharmaceutically acceptable salt of fluoxetine.

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