Process for the preparation of paroxetine substantially free of alkoxy impurities

Abstract

The present invention is directed to methods for preparing intermediates useful in the synthesis of paroxetine wherein the intermediates are substantially free of alkoxy impurities as well as to methods for preparing paroxetine and pharmaceutically acceptable salts thereof substantially free of alkoxy impurities. The alkoxy impurity is reacted with an ether cleaving agent to generate the corresponding phenol, which is separated, yielding the desired product substantially free of alkoxy impurities. Paroxetine intermediates such as PMA, paroxetine, and pharmaceutically acceptable salts thereof substantially free of alkoxy impurities also form part of the present invention.

1 - 22 . (canceled)  
     
     
         23 . A compound selected from the group consisting of PMA, paroxetine base, and a pharmaceutically acceptable salt of paroxetine wherein said compound contains less than about 0.5% of the corresponding alkoxy impurity as measured by HPLC.  
     
     
         24 . The compound of  claim 23 , wherein the pharmaceutically acceptable salt is paroxetine hydrochloride.  
     
     
         25 . The compound of  claim 23 , wherein the pharmaceutically acceptable salt is paroxetine hydrochloride isopropanolate.  
     
     
         26 . The compound of  claim 23 , wherein said compound contains less than about 0.1% of the corresponding alkoxy impurity as measured by HPLC.  
     
     
         27 . The compound of  claim 23 , wherein said compound contains less than about 0.05% of the corresponding alkoxy impurity as measured by HPLC.  
     
     
         28 . A pharmaceutical composition comprising an effective amount of a compound selected from the group consisting of PMA, paroxetine base, and a pharmaceutically acceptable salt of paroxetine wherein said compound contains less than about 0.5% of the corresponding alkoxy impurity as measured by HPLC, and a pharmaceutically acceptable excipient.  
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein the pharmaceutically acceptable salt is paroxetine hydrochloride.  
     
     
         30 . The pharmaceutical composition of  claim 28 , wherein the pharmaceutically acceptable salt is paroxetine hydrochloride isopropanolate.  
     
     
         31 . A method of inhibiting the re-uptake of serotonin to a patient in need thereof comprising administering the compound of  claim 23  to the patient.  
     
     
         32 . A method of inhibiting the re-uptake of serotonin to a patient in need thereof comprising administering the pharmaceutical composition of  claim 28  to the patient.  
     
     
         33 . Paroxetine or a pharmaceutically acceptable salt thereof substantially free of alkoxy impurities.