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 .- 18 . (canceled) 
     
     
         19 . An optically active 1-aroylnipecotamide derivative represented by the following formula (4): 
       
         
           
           
               
               
           
         
         wherein, * indicates an asymmetric carbon atom; Ar represents a phenyl group, a p-methylphenyl group or a p-chlorophenyl group. 
       
     
     
         20 . An optically active 1-aroyl-3-aminopiperidine derivative represented by the following formula (5): 
       
         
           
           
               
               
           
         
         wherein, * indicates an asymmetric carbon atom; Ar represents a phenyl group, a p-methylphenyl group or a p-chlorophenyl group. 
       
     
     
         21 . An optically active 1-aroyl-3-(protected amino)piperidine derivative represented by the following formula (6): 
       
         
           
           
               
               
           
         
         wherein, * indicates an asymmetric carbon atom; Ar represents a phenyl group, a p-methylphenyl group or a p-chlorophenyl group; R 2  represents a benzoyl group, a p-methylbenzoyl group, a p-chlorobenzoyl group or a tert-butoxycarbonyl group.