Originator
Vadilex,Carriere,France,1972
Manufacturing Process
The initial steps involve reacting benzyl chloride with 4-
hydroxypropiophenone. The benzyloxypropiophene thus obtained is first
brominated and then reacted with 4-benzylpiperidine to give 1-(pbenzyloxyphenyl)-2-(4-benzyl-piperidino)propan-1-one.
The neutral tartrate may be prepared directly by reduction of 1-(pbenzyloxyphenyl)-2-(4-benzyl-piperidino)propan-1-one. For the reduction, a
mixture of 175 g of ketone (0.425 mol) and 32 g of tartaric acid (0.213 mol)
is hydrogenated at 50°C under pressure of 50 kg/cm2 in 440 ml of methanol
in the presence of 12 g of palladium on charcoal.
The catalyst is filtered off at elevated temperature, and the filtrate is
concentrated by evaporation under reduced pressure to a volume of 300 ml
and added in a thin stream to 2.5 liters of diethyl ether with mechanical
agitation. The precipitate is separated, washed with diethyl ether and dried in
vacuo at 80° to 85°C for several hours. 325 g (96% yield) of the neutral
tartrate of 1-(p-hydroxyphenyl)-2-(4-benzyl-piperidino)propan-1-ol are
obtained.