Process for preparing telmisartan

Abstract

Provided are processes for preparing telmisartan-alkyl ester and telmisartan using environmentally friendly organic solvents that are easily removed from the reaction mixture, wherein a telmisartan alkyl ester is isolated and hydrolyzed to form telmisartan or the telmisartan is prepared using a synthesis in a single reaction vessel.

1 . (canceled) 
   
   
       2 . A process for the preparation of telmisartan in a single reaction vessel comprising the steps of
 (a) combining BIM of formula III, a BMBP alkylester of formula IV, an inorganic base and a ketone solvent, to obtain a mixture;   (b) heating the mixture obtained in step (a) to a temperature of about 55° C. about 120° C.;   (c) maintaining the mixture obtained in step (b) for about 6 hours to about 24 hours, to obtain telmisartan salt of formula V;   
     
       
         
         
             
             
         
       
       (d) separating the organic phase containing telmisartan salt of formula V, from the aqueous phase; 
       (e) converting telmisartan salt of formula V to telmisartan of formula I; and 
       (f) recovering telmisartan of formula I,
 wherein, 
 R is a straight or branched chain C 1 -C 4  alkyl; 
 M is a metal cation. 
 
     
   
   
       3 . The process of  claim 2 , wherein the straight or branched chain C 1 -C 4  alkyl is methyl. 
   
   
       4 - 5 . (canceled) 
   
   
       6 . The process of  claim 2 , wherein water is added to the ketone solvent in step (a). 
   
   
       7 . (canceled) 
   
   
       8 . The process of  claim 2 , wherein the ketone is methylethylketone, methylisobutylketone or acetone. 
   
   
       9 - 10 . (canceled) 
   
   
       11 . The process of  claim 8 , wherein the ketone is acetone. 
   
   
       12 . The process of  claim 2 , wherein the amount of BIM used in step (a) is of about 0.8 to about 1.5 mole equivalent per mole equivalent of BMBP. 
   
   
       13 . The process of  claim 12 , wherein the amount of BIM used in step (a) is of about 0.9 to about 1 mole equivalent per mole equivalent of BMBP. 
   
   
       14 . The process of  claim 2 , wherein the inorganic base is selected from the group consisting of a metal hydroxide and a metal carbonate. 
   
   
       15 . The process of  claim 14 , wherein the metal hydroxide is sodium hydroxide, potassium hydroxide, cesium hydroxide, barium hydroxide, magnesium hydroxide, calcium hydroxide or strontium hydroxide. 
   
   
       16 . The process of  claim 14 , wherein the metal carbonate is sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or cesium carbonate. 
   
   
       17 . The process of  claim 14 , wherein the inorganic base is either potassium carbonate or sodium hydroxide. 
   
   
       18 . The process of  claim 2 , wherein an aqueous solution of an inorganic base is used in step (a). 
   
   
       19 - 21 . (canceled) 
   
   
       22 . The process of  claim 1  and  2 , wherein the temperature of step (c) is of about 78° C. to about 120° C. 
   
   
       23 . The process of  claim 2 , wherein the telmisartan salt of formula V is converted to telmisartan by adding an acid to the organic phase obtained in step (d). 
   
   
       24 . The process of  claim 23 , wherein the acid is added to obtain a pH of less than about 6. 
   
   
       25 . The process of  claim 24 , wherein the acid is added to obtain a pH of about 4 to about 6. 
   
   
       26 . The process of  claim 23 , wherein the acid is selected from the group consisting of trifluoroacetic acid sulfuric acid and acetic acid. 
   
   
       27 . The process of  claim 26 , wherein the acid is acetic acid. 
   
   
       28 - 30 . (canceled)