Compounds and methods for preparing methanesulfonamides

Abstract

A process for preparing (S)-(-)-N-[4-[4-[ethyl(6-fluoro-6-methylheptyl)amino]-1-hydroxy]phenyl]methanesulfonamide hemifumarate salt, which comprises reacting N-[4[(2S)-tetrahydro-5-hydroxy-2-furanyl]phenyl]methanesulfonamide (IIa) with fluoroamine (III) in the presence of triacetoxyborohydride and ethyl acetate to provide [4-[4-[ethyl(6-fluoro-6-metylheptyl)amino]-1-hydroxy]phenyl]methanesulfonamide (I) anll then converting I into the hemifumarate salt Ia. A process for preparing IIa is also claimed as well as intermediates IIa-lId.

1 . A process for preparing (S)-(-)-N-[4-[-4-(ethyl(6-fluoro-6-methyl-heptyl)amino]-1-hydroxybutyl]phenyl] methanesulfonamide (I) which comprises reacting N-[4[(2S)-tetrahydro-5-hydroxy-2-furanyllphenyl]methanesulfonamide (Ila) with flouroamine (III)in the presence of triacetoxy borohydride and ethyl acetate.  
     
     
         2 . A process according to  claim 1 , wherein N- [4 [ (2S) -tetrahydro-5-hydroxy-2-furanyl]phenyl] methanesulfonamide is prepared by (l)subjecting 4-[(methylsulfonyl)amino]- -oxobenzenebutanoic acid(IIe) to a Fisher esterification to obtain methyl 4[(methylsulfonyl)amino]- -oxobenzenebutanoate (IId), (2) reducing methyl 4-[(methylsulfonyl)amino]- -oxobenzenebutanoate with (-)-DIP-CI to obtain methyl ( S)-4-[methylsulfonyl)amino] - -hydroxybenzenebutanoate (IIc), (3) subjecting methyl( S)-4-[methylsulfonyl)aminol- -hydroxybenzenebutanoate to lactonization with an acid catalyst in the presence of a solvent at a temperature of between −10° to 23° C. to obtain N-[4-[(2S)-tetrahydro-5-oxo-2-furanyl]phenyl]methanesulfonamide (Ilb) and reacting N-(4-[(2S)-Tetrahydro-5-oxo-2-furanyl]phenyl]methanesulfonamide with DIBAL-H in the presence of a solvent and at a temperature of between −35 to −30 C obtain N-[4-[(2S)-tetrahydro-5-hydroxy-2-furanyl]phenyl]methanesulfonamide.  
     
     
         3 . A process according to  claim 1 , wherein (S)-(-)-N-[4-[-4-[ethyl(6-fluoro-6-methyl-heptyl)amino]-1-hydroxybutyllphenyl] methanesulfonamide is further reacted with fumaric acid to obtain (S)-(-)-N-[4-(-4-[ethyl(6-fluoro -6-methyl-heptyl)amino]-1-hydroxybutyl]phenyl] methanesulfonamide hemifumarate salt.  
     
     
         4 . A compound having the formula  
       
         
           
           
               
               
           
         
       
       wherein R is selected from the group consisting of 
 (a) —C(O)—(CH 2 ) 2 —C(O)OCH 3    
 (b) —C(OH)—(CH 2 ) 2 —C(O)OCH 3    
 (c) 5-oxo-2-furanyl-  
 (d) 5-hydroxy-furanyl-.  
 
     
     
         5 . A compound according to  claim 4 , wherein R is selected from the group consisting of —C(O)—(CH 2 ) 2 — C(O)OCH 3  and —CH(OH)—(CH 2 ) 2 —C(O)OCH 3 .  
     
     
         6 . A compound according to  claim 5 , methyl 4-((methylsulfonyl)amino]- -oxobenzenebutanoate.  
     
     
         7 . A compound according to  claim 5 , methyl ( S)-4-[methylsulfonyl)amino]- -hydroxybenzene-butanoate.  
     
     
         8 . A compound according to  claim 4 , wherein R is selected from the group consisting of 5-oxo-2-furanyl- and 5-hydroxy-furanyl.  
     
     
         9 . A compound according to  claim 8 , N-[4-[(2S)tetrahydro-5-oxo-2-furanyl]phenyl]methane-sulfonamide.  
     
     
         10 . A compound according to  claim 8 , N-[4-[(2S)-tetrahydro-5-hydroxy-2-furanyl]phenyl]methane-sulfonamide.  
     
     
         11 . A fluoroamine compound, N-ethyl-6methyl-6-fluoroheptane amine.  
     
     
         12 . A process for preparing N-ethyl-6-methyl-6-fluoroheptane amine which comprises reacting a solution of 6-bromo-2-fluoro-2-methylheptane with aqueous ethylamine in the presence of a solvent and recovering the N-ethyl-6-methyl-6-fluoroheptane amine from the reaction mixture.