Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates

Abstract

wherein, R1 and R2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR3R4, OR5, or SR5, where R3 and R4 are individually selected from acyl or sulfonyl, and where R5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

1 - 14 . (canceled) 
     
     
         15 . A method of preparing a 6-fluoro-3-[1-(3-substituted propyl)piperidin-4-yl]-1,2-benzoxazole of the following formula 
       
         
           
           
               
               
           
         
       
       comprising
 (i) alkylating 1,3,2-dioxathiane 2,2-dioxide having the formula 
 
       
         
           
           
               
               
           
         
       
       with a phenolic compound of the formula 
       
         
           
           
               
               
           
         
       
       in the presence of base selected from potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide or calcium hydroxide, to form the corresponding alkylation compound of the formula 
       
         
           
           
               
               
           
         
       
       wherein Q is potassium, sodium, magnesium or calcium;
 (ii) hydrolyzing the alkylation compound of step (i) with aqueous acid to obtain the corresponding hydroxyl compound of formula 
 
       
         
           
           
               
               
           
         
         (iii) converting the compound of formula 
       
       
         
           
           
               
               
           
         
       
       of step (ii) to the corresponding alkylating agent compound of formula 
       
         
           
           
               
               
           
         
       
       wherein LG is selected from the group consisting of aryl sulfonate or alkyl sulfonate; and
 (iv) alkylating the compound of formula 
 
       
         
           
           
               
               
           
         
       
       of step (iii) with the compound of formula 
       
         
           
           
               
               
           
         
       
       in the presence of a base selected from potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide or calcium hydroxide. 
     
     
         16 . The process of claim  1  wherein the base of steps (i) and (iv) is potassium carbonate. 
     
     
         17 . The process of claim  1  wherein LG is methylsulfonate. 
     
     
         18 . The process of claim  1  wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         19 . The process of claim  1  wherein Y is