Method for preparing high-purity fesoterodine fumarate

Abstract

A process is described for preparing fesoterodine fumarate comprising the salification reaction of fesoterodine with fumaric acid in an organic solvent, preferably a ketone, at a temperature not greater than 45° C. Such process allows obtaining products with high yields and purities, and in particular a product having a content of (2E)-4-[(3-(3-diisopropylamino-1-phenylpropyl)-4-(2-isobutyroyloxyphenyl)methoxy]-4-oxobut-2-enoic acid less than or equal to 0.15% by mole.

1 . Process for preparing fesoterodine fumarate comprising reacting fesoterodine with fumaric acid, wherein said reaction step is carried out in at least one organic solvent at a temperature not higher than 45° C. 
     
     
         2 . Process according to  claim 1 , wherein said temperature is comprised between 30 and 40° C. 
     
     
         3 . Process according to  claim 2 , wherein said temperature is about 35° C. 
     
     
         4 . Process according to  claim 1 , further comprising heating a mixture of fesoterodine and fumaric acid in said at least one organic solvent until complete dissolution, and cooling the solution thus obtained at a temperature lower than 25° C. 
     
     
         5 . Process according to  claim 4 , wherein said heating step is carried out for a period comprised between 10 minutes and two hours. 
     
     
         6 . Process according to  claim 5 , wherein said heating step is carried out for a period comprised between 30 minutes and one hour. 
     
     
         7 . Process according to  claim 4 , wherein said cooling step is carried out at a temperature comprised between 5 and 20° C. 
     
     
         8 . Process according to  claim 7 , wherein said cooling step is carried out at a temperature comprised between 15 and 20° C. 
     
     
         9 . Process according to  claim 1 , wherein said at least one organic solvent is a polar aprotic organic solvent. 
     
     
         10 . Process according to  claim 1 , wherein said at least one organic solvent is a ketone. 
     
     
         11 . Process according to  claim 10 , wherein said ketone has from three to six carbon atoms. 
     
     
         12 . Process according to  claim 10 , wherein said ketone is methylethylketone. 
     
     
         13 . Process according to  claim 1 , wherein said fumaric acid is used in molar ratios comprised between 0.9 and 1.5 with respect to fesoterodine. 
     
     
         14 . Process according to  claim 13 , wherein said fumaric acid is used in molar ratios comprised between 1.0 and 1.1 with respect to fesoterodine. 
     
     
         15 . Process according to  claim 1 , wherein said fesoterodine is used in a weight/volume ratio comprised between 2 and 50 with respect to said at least one organic solvent. 
     
     
         16 . Process according to  claim 15 , wherein said fesoterodine is used in a weight/volume ratio comprised between 3 and 10 with respect to said at least one organic solvent. 
     
     
         17 . Process according to  claim 1 , wherein the fesoterodine fumarate thus obtained is filtered, washed, dried under vacuum and/or micronized. 
     
     
         18 . Process according to  claim 17 , wherein the fesoterodine fumarate is micronized until obtaining a PSD with d (0.9)≦20 micron. 
     
     
         19 . Fesoterodine fumarate having a content of (2E)-4-[(3-(3-diisopropylamino-1-phenylpropyl)-4-(2-isobutyroyloxyphenyl)methoxy]-4-oxobut-2-enoic acid less than or equal to 0.15% by mole. 
     
     
         20 . Micronized fesoterodine fumarate having a content of (2E)-4-[(3-(3-diisopropylamino-1-phenylpropyl)-4-(2-isobutyroyloxyphenyl)methoxy]-4-oxobut-2-enoic acid less than or equal to 0.15% by mole and a PSD with d (0.9)≦20 micron.