Processes and intermediates for resolving piperidyl acetamide stereoisomers

Abstract

Processes and intermediates for preparing 2-substituted piperidines such as 2-substituted d-threo piperidines are provided, including processes and intermediates for resolution of piperidyl acetamide stereoisomers.

1 - 14 . (Cancelled)  
     
     
         15 . A synthetic process comprising the steps of: 
 providing a mixture of said d,l-threo piperidyl acetamide stereoisomers having formulas:                           wherein R 1  is aryl having about 6 to about 28 carbon atoms;    reacting said stereoisomers with an acid resolving agent having the formula      HO 2 CCH[OC(O)R 3 ]CH[OC(O)R 3 ]CO 2 H     wherein each R 3 , independently, is aryl having 6 to about 28 carbon atoms or aralkyl having 7 to about 28 carbon atoms in an organic solvent comprising an alcohol, an alkyl alkanoate, a ketone, or an ether, and thereby forming acid salts; and    physically isolating said acid salts.    
     
     
         16 . The process of  claim 15  wherein R 1  is phenyl.  
     
     
         17 . The process of  claim 15  wherein said solvent is an alkyl alcohol having 1 to about 5 carbon atoms.  
     
     
         18 . The process of  claim 15  wherein said alkyl alcohol is isopropanol.  
     
     
         19 . The process of  claim 15  further comprising reacting said d-threo acid salts with aqueous base to form said d-threo piperidine acetamide.  
     
     
         20 . The process of  claim 19  further comprising reacting said d-threo piperidine acetamide with an alcohol having 1 to about 5 carbon atoms in the presence of acid to form a d-threo piperidine acetate.  
     
     
         21 . The process of  claim 15  wherein said d, l-threo piperidyl acetamide stereoisomers are prepared by reacting a pyridine having formula:  
       
         
           
           
               
               
           
         
         with hydrogen in an alkanoic acid having 1 to about 10 carbon atoms in the presence of a catalyst to provide a mixture of threo and erythro piperidyl stereoisomers; and  
         contacting said erythro stereoisomers with organic base, thereby converting said erythro piperidyl stereoisomers to threo piperidyl stereoisomers.  
       
     
     
         22 . The product of the process of  claim 15.