Process for the Preparation of (3R,4R)-(1-BENZYL-4-METHYLPIPERIDIN-3-YL)-METHYLAMINE

Abstract

The present disclosure is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: (a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The disclosure is also related to novel intermediates: wherein R, R′ and X are as described in the specification.

1 . The compound of the formula (IVa) and salts thereof, 
       
         
           
           
               
               
           
         
         wherein R represents C3-C10 alkyl, aryl or substituted aryl, but not including iso-propyl, t-butyl and phenyl. 
       
     
     
         2 . A compound of formula (Va). 
       
         
           
           
               
               
           
         
         wherein R represents alkyl, aryl or substituted aryl; R′ represents aryl or substituted aryl group; and X represents halides groups selected from chloro, bromo, iodo or any leaving group selected from tosyloxy or mesyloxy.