Method for preparing n-aminopiperidine and its salts

Abstract

The invention concerns a novel method for preparing N-aminopiperidine of formula (I):

1 . A process for the preparation of N-aminopiperidine of formula (I):  
     
       
         
         
             
             
         
       
     
     or a salt thereof, comprising the steps of: 
 a) reacting a carbazate of formula (II):  
   NH 2 —NH—COOR  (II)  
 in which R represents a (C 1 -C 6 )alkyl group, a phenyl or a benzyl, with a 1,5-dihalopentane of formula (III):  
   Hal—(CH 2 ) 5 —Hal  (III)  
 in which Hal represents a halogen atom to obtain piperidin-1-ylcarbamate of formula (IV):  
                     
 in which R is as defined above;  
 b) treating the piperidin-1-ylcarbamate thus obtained in acidic medium or in basic medium to produce the compound of formula (I); and  
 c) optionally reacting the compound of formula (I) taken in a solvent with a suitable inorganic or organic acid to form the salt of the compound of formula (I).  
 
   
   
       2 . The process according to  claim 1 , wherein in step a), the reaction is carried out in a solvent chosen from acetonitrile or toluene at a temperature in the range of from about ambient temperature and about reflux temperature of the solvent.  
   
   
       3 . The process according to  claim 1 , wherein in step b), the reaction is carried out using an acid chosen from hydrochloric acid or hydrobromic acid in a solvent chosen from water or ethanol and at a temperature in the range of from about ambient temperature and about reflux temperature of the solvent.  
   
   
       4 . The process according to  claim 1 , wherein in step b), the reaction is carried out using a base chosen from potassium hydroxide or sodium hydroxide in a solvent chosen from water or ethanol and at a temperature in the range of from about ambient temperature and about reflux temperature of the solvent.  
   
   
       5 . The process according to  claim 2 , wherein in step b), the reaction is carried out using an acid chosen from hydrochloric acid or hydrobromic acid in a solvent chosen from water or ethanol and at a temperature in the range of from about ambient temperature and about reflux temperature of the solvent.  
   
   
       6 . The process according to  claim 2 , wherein in step b), the reaction is carried out using a base chosen from potassium hydroxide or sodium hydroxide in a solvent chosen from water or ethanol and at a temperature in the range of from about ambient temperature and about reflux temperature of the solvent.  
   
   
       7 . The process according to claims  1 , wherein, in step a), a compound of formula (II) in which R represents an ethyl radical is treated with a compound of formula (III) in which Hal represents a bromine atom, in acetonitrile, by heating at reflux of the solvent.  
   
   
       8 . The process according to  claim 1 , wherein, in step b), the compound of formula (IV) in which R represents an ethyl radical is treated with sodium hydroxide in water by heating at reflux of the solvent.  
   
   
       9 . The process according to  claim 1 , wherein in step c), the compound of formula (I) is reacted with an inorganic acid to form the salt.  
   
   
       10 . The process according to  claim 9 , wherein the inorganic acid is chosen from hydrochloric acid or hydrobromic acid.  
   
   
       11 . The process according to  claim 1 , wherein in step c), the compound of formula (I) is reacted with an organic acid to form the salt.  
   
   
       12 . The process according to  claim 11 , wherein the organic acid is oxalic acid.  
   
   
       13 . The process according to  claim 1 , wherein in step c), the solvent is methyl tert-butyl ether.  
   
   
       14 . The process according to  claim 1 , wherein in step c), the reaction is carried out in the temperature range of from about 0° C. to about 40° C.  
   
   
       15 . The process according to  claim 1 , wherein in step c), the reaction is carried out at a temperature of about 25° C.  
   
   
       16 . The process according to  claim 1 , wherein a salt of the compound of formula (I) chosen from the hydrobromide, the hydrochloride or the oxalate is prepared.  
   
   
       17 . The process according to  claim 1 , wherein the hydrobromide of the compound of formula (I) is prepared in methyl tert-butyl ether.