Process for the production of paroxetine

#This application claims the benefit of priority under 35 U.S.C. §119 from The Netherlands patent application serial number 1017421, filed Feb. 21, 2001, the entire contents of which are incorporated herein by reference.

#The present invention relates to a process for preparing the pharmaceutically active compound paroxetine.

#Pharmaceutical products with antidepressant and anti-Parkinson properties are described in U.S. Pat. No. 4,007,196. An especially important compound is paroxetine, the (−) trans isomer of 4-(p-fluorophenyl)-3-(3,4-methylenedioxy-phenoxymethyl)-piperidine of the formula (1).

#Paroxetine Methane Sulfonate

#a) Paroxetine Phenylcarbamate

#The reaction vessel was charged with 17.4 kg of N-methylparoxetine (containing approx. 5% of water) and 58 liter of toluene. The reaction mixture was heated to reflux and rests of water were removed by azeotropic distillation using a Dean-Stark receiver. Under reflux, 9.1 kg of phenyl chloroformate was added in 30 minutes and stirring continued at reflux for 1.5 hours. 0.8 liter of triethylamine was added and the mixture was heated under reflux for next 30 minutes. The solution was concentrated to approx. 30 liter volume by distillation at diminished pressure (30 mbar) and cooled to ambient temperature.