Novel processes for the preparation of (r)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol

Abstract

The present invention provides various processes for the preparation of (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol.

1 . A process for preparing 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine comprising the step of reacting lithiated veratrole with 4-pyridinecarboxaldehyde in the presence of a suitable aprotic solvent selected from the group consisting of hexane, tetrahydrofuran, toluene and a mixture thereof at a temperature from about −25° C. to about 30° C.  
   
   
       2 . The process according to  claim 1  wherein the aprotic solvent is toluene.  
   
   
       3 . The process according to  claim 1  wherein the aprotic solvent is a mixture of toluene and tetrahydrofuran.  
   
   
       4 . The process according to  claim 1  wherein the aprotic solvent is a mixture of toluene and hexane.  
   
   
       5 . The process according to  claim 1  wherein the temperature is from about −10° C. to about 30° C.  
   
   
       6 . The process according to  claim 1  wherein the temperature is from about 0° C. to about 30° C.  
   
   
       7 . The process according to  claim 1  wherein the temperature is from about 10° C. to about 30° C.  
   
   
       8 . The process according to  claim 1  wherein the temperature is from about 20° C. to about 30° C.  
   
   
       9 . A compound which is 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine.