PROCESS FOR THE PREPARATION OF 1-(4-HYDROXYPHENYL)-2- (4-BENZYLPIPERIDINO)-1-PROPANOL AND ACID-ADDITION SALTS THEREOF

摘要

Title: A NEW PROCESS FOR THE PREPARATION OF 1-(4-HYDROXYPHENYL)-2-(4-BENZYLPIPERIDINO)-1-PROPANOL AND ACID-ADDITION SALTS THEREOF A new valuable process for the preparation of 1-(4-hydroxy-phenyl)-2-(4-benzylpiperidino)-1-propanol (i.e. ifenprodil) and acid-addition salts thereof, characterized by brominating 4'hydroxypropiophenone in a single or mixed solvent selected from the group consisting of methanol, ethanol and a saturated aliphatic ether, removing hydrogen bromide formed in the course of the bromination, adding 4-benzylpyridine to the reaction mixture, heating the reaction mixture under reflux in a single or mixed solvent selected from the group consisting of methanol and ethanol, and then subjecting the resultant reaction mixture to catalytic reduction to form 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol hydrobromide in the reaction mixture. The end product (i.e. ifenprodil) can be obtained according to this new process in a high yield of about 80% within 14 hours from the starting material in a single reaction container throughout the process, without introducing protective benzyl group into the starting material prior to the bromination.