Process for the preparation of 1-(4-hydroxyphenyl)-2-...

C - Chemistry – Metallurgy – 07 – D

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C07D 211/22 (2006.01) C07D 211/14 (2006.01)

Patent

CA 1141387

Title: A NEW PROCESS FOR THE PREPARATION OF 1-(4-HYDROXYPHENYL)- 2-(4-BENZYLPIPERIDINO)-1-PROPANOL AND ACID-ADDITION SALTS THEREOF ABSTRACT OF THE DISCLOSURE 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 bromi- nation, 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 reduc- tion to form 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol hydrobromide in the reaction mixture. The end product (i.e. ifen- prodil) 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 intro- ducing protective benzyl group into the starting material prior to the bromination. - 1 -

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