Purification process

Abstract

Purification process for the preparation of the allylamine pharmaceutical terbinafine of formula I in free base form or acid addition salt form, by distilling crude terbinafine base, preferably by short path distillation, e.g. at a temperature above 100° C. and reduced pressure, e.g. 0.2 mbar, and recovering the purified product in free base or acid addition salt form.

1 . A process for the purification of terbinafine which comprises subjecting crude terbinafine in free base form to distillation and recovering the resultant product in free base or acid addition salt form.  
     
     
         2 . A process according to  claim 1  which comprises short path distillation.  
     
     
         3 . A process according to  claim 1  wherein distillation is effected at a temperature above 100° C. and under reduced pressure.  
     
     
         4 . A process according to  claim 1  wherein the crude terbinafine is prepared using a palladium- and/or a copper-containing catalyst.  
     
     
         5 . A process according to  claim 4  wherein the purified product contains less than 2 ppm palladium and/or less than 1 ppm copper.  
     
     
         6 . A process according to  claim 4  wherein the crude terbinafine contains more than 2 ppm palladium and/or more than 1 ppm copper, and the resultant purified product contains less than 2 ppm palladium and/or less than 1 ppm copper.  
     
     
         7 . A process according to  claim 1  wherein at least 5 kg purified product in free base form is prepared per distillation batch or run, preferably at least 50 kg, especially at least 200 kg.  
     
     
         8 . A process according to  claim 1  wherein the crude terbinafine in free base form is prepared by reaction of (E)-N-(3-halo-2-propenyl)-N-methyl-N-(1-naphthylmethyl)amine with 3,3-dimethyl-1-butyne in the presence of a palladium and/or a copper catalyst.  
     
     
         9 . Purified terbinafine in free base or acid addition salt form whenever prepared by a process according to any one of claims  1 .  
     
     
         10 . Terbinafine in free base or acid addition salt form comprising less than 2 ppm palladium and/or less than 1 ppm copper, whenever obtained from a crude product in free base form comprising more than 2 ppm palladium and/or more than 1 ppm copper.