Process for preparing phenoxyphenylsulfonyl halides

Abstract

A process for preparing phenoxyphenylsulfonyl halides, which are useful intermediates for the preparation of matrix metalloproteinase inhibitors.

1 . A compound of the formula  
                   
       wherein R is H, Li, Na, K, Mg, or NH 4 .  
     
     
         2 . A compound of the formula  
                   
       wherein 
 m is an interger from 1-3;  
 R 2  is fluoro, chloro, bromo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or perfluoro(C 1 -C 3 )alkyl.  
 
     
     
         3 . A compound according to    claim 2    wherein R 2  is fluoro.  
     
     
         4 . A compound according to    claim 3    wherein R 2  is in the 4-position of the phenyl ring.  
     
     
         5 . A process for preparing a compound of the formula  
                   
       wherein 
 m is an interger from 1-3;  
 R 2  is fluoro, chloro, bromo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or perfluoro(C 1 -C 3 )alkyl;  
 comprising, reacting a compound of the formula  
                 
 
 wherein  
 R 3  is fluoro, chloro or bromo; and  
 R 4  is chloro or bromo;  
 with a compound of the formula  
                 
 
 wherein  
 m is an interger from 1-3; and  
 R 2  is fluoro, chloro, bromo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or perfluoro(C 1 -C 3 )alkyl,  
 in the presence of a base and a solvent at a temperature from 0° C. to about 150° C.  
 
     
     
         6 . A process according to    claim 5    wherein said base is potassium t-butoxide and said solvent is N-methylpyrrolidinone.  
     
     
         7 . A process according to    claim 5    further comprising, reacting said compound of formula III with a base in a solvent at a temperature from about 50° C. to about 100° C. to form a compound of the formula  
                 
 
       wherein 
 m is an interger from 1-3;  
 R is H, Li, Na, K or NH 4 ; and  
 R 2  is fluoro, chloro, bromo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or perfluoro(C 1 -C 3 )alkyl.  
 
     
     
         8 . A process according to    claim 7    wherein said base is sodium hydroxide and said solvent is ethanol.  
     
     
         9 . A process according to    claim 7    further comprising reacting a compound of the formula  
                 
 
       wherein 
 m is an interger from 1-3;  
 R is H, Li, Na, K or NH 4 , and  
 R 2  is fluoro, chloro, bromo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or perfluoro(C 1 -C 3 )alkyl;  
 with a halogenating agent in a solvent at a temperature from about 0° C. to about 80° C. to form a compound of the formula  
                 
 
 wherein R 1  is halo and m is an integer from 1-3.  
 
     
     
         10 . A process according to    claim 9    wherein R 1  is chloro.  
     
     
         11 . A process according to    claim 9    wherein R 2  is fluoro.  
     
     
         12 . A process according to    claim 9    wherein R 2  is in the 4-position of the phenyl ring  
     
     
         13 . A process according to    claim 9    wherein said halogenating agent is thionyl chloride.  
     
     
         14 . A process according to    claim 9    further comprising the addition of a catalyst and a solvent.  
     
     
         15 . A process according to    claim 14    wherein said catalyst is dimethylformamide and said solvent is toluene.