Method for producing optically active 3-aminopiperidine or salt thereof

Abstract

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.

1 - 21 . (canceled) 
     
     
         22 . A method for producing an optically active 1-aroyl-3-(protected amino)piperidine derivative, comprising the steps of:
 producing an optically active 1-aroyl-3-aminopiperidine derivative represented by the following formula (5):   
       
         
           
           
               
               
           
         
         
           wherein * indicates an asymmetric carbon atom and Ar represents an optionally substituted aryl group having 6 to 15 carbon atoms, 
           by Hofmann rearrangement at the amide group of an optically active 1-aroylnipecotamide derivative represented by the following formula (4): 
         
       
       
         
           
           
               
               
           
         
         
           wherein * and Ar mean the same as the above; and 
         
         aroylating or carbamating the amino group of formula (5) for crystallization or extraction to isolate the optically active 1-aroyl-3-(protected amino)piperidine derivative represented by the following formula (6): 
       
       
         
           
           
               
               
           
         
         
           wherein * and Ar mean the same as the above; R 2  represents an optionally substituted aroyl group having 7 to 15 carbon atoms, an alkyloxycarbonyl group having 2 to 15 carbon atoms, an alkenyloxycarbonyl group having 3 to 15 carbon atoms, an aryloxycarbonyl group having 7 to 15 carbon atoms, or an aralkyloxycarbonyl group having 8 to 15 carbon atoms. 
         
       
     
     
         23 . A method for producing an optically active 3-aminopiperidine or salt thereof represented by the following formula (7): 
       
         
           
           
               
               
           
         
         wherein * indicates an asymmetric carbon atom, 
         comprising a step of hydrolyzing the compound (6) produced by the method according to  claim 22 .