Methods for preparing sulfonamide compounds

Abstract

Methods for preparing substituted phenylsulfonamide compounds of the following structure are provided: or a pharmaceutically acceptable salt thereof, wherein, R 1 -R 7 are defined herein. Also provided are methods for preparing compounds of the following structure: wherein, R 9 , m, n, p, r, and s are defined herein.

1 . A method of preparing an ester of the structure: 
     
       
         
         
             
             
         
       
       wherein:
 R 9  is alkyl; 
 n and p are, independently, 0 to 20; 
 m, q, r, and s are, independently, 0 to 2; 
 provided that m+q=2 and r+s=2; 
 
       said method comprising reacting CF 3 (CH m F q ) n CHO and an organophosphorus compound of the structure: 
     
     
       
         
         
             
             
         
       
       wherein:
 R 8  is aryl or alkoxy. 
 
     
   
   
       2 . The method according to  claim 1 , wherein R 9  is CH 2 CH 3 . 
   
   
       3 . The method according to  claim 1 , wherein n and p are 0. 
   
   
       4 . The method according to  claim 1 , wherein said CF 3 (CH m F q ) n CHO reagent is ethylchloroformate. 
   
   
       5 . The method according to  claim 1 , wherein said organophosphorus compound is 4,4,4-trifluoro-2-(triphenyl-λ 5 -phosphanylidene)-butyric acid ethyl ester. 
   
   
       6 . The method according to  claim 1 , wherein said ester is 4,4,4-trifluoro-2-(2,2,2-trifluoro-ethyl)-but-2-eonic acid ethyl ester. 
   
   
       7 . A method of preparing an aldehyde of the structure: 
     
       
         
         
             
             
         
       
       wherein:
 n and p are, independently, 0 to 20; 
 m, q, r, and s are, independently, 0 to 2; 
 provided that m+q=2 and r+s=2; 
 
       said method comprising reacting a reducing agent and an amide of the structure: 
     
     
       
         
         
             
             
         
       
       wherein:
 R 11  and R 12  are, independently, alkyl. 
 
     
   
   
       8 . The method according to  claim 7 , wherein said reducing agent is DIBAL-H. 
   
   
       9 . The method according to  claim 7 , wherein n and p are 0. 
   
   
       10 . The method according to  claim 7 , wherein R 11  and R 12  are CH 3 , n is 0, and p is 0. 
   
   
       11 . The method according to  claim 7 , wherein said aldehyde is 4,4,4-trifluoro-2-(2,2,2-trifluoro-ethyl)-butyraldehyde. 
   
   
       12 . The method according to  claim 7 , wherein said amide is 4,4,4-trifluoro-N-methoxy-N-methyl-2-(2,2,2-trifluoro-ethyl)-butyramide.