Process for the preparation of enantiopure pyrrolidin-2-one derivatives

Abstract

The present invention relates to a process for the preparation of enantiopure intermediates useful in the synthesis of valuable pharmaceutically active compounds, e.g. MAOB inhibitors, and to novel intermediates of formulae I and II wherein R 21 , R 22 , R 23 and R 24 are as defined in the description and claims.

1 . A compound of formula I  
       
         
           
           
               
               
           
         
         wherein  
         R 21 , R 22  and R 23  are each independently hydrogen or halogen; and  
         R 24  is hydrogen, methyl or halogen.  
       
     
     
         2 . A derivative of a compound of formula I according to  claim 1  which derivative is selected from carboxamides, N-substituted carboxamides, N,N-disubstituted carboximides, carboxamidines, N-hydroxy carboxamidines, carboxylic acid hydroxamides, carboxylic acid hydrazides, carbonitriles, carbaldehydes, ketones, isocyanates, carbamates, ureas, N-substituted ureas, N,N-disubstituted ureas, prim., sec. and tert. amines, N-amides, guanidines, aminomethyl, hydroxymethyl, derivatives, and ester derivatives.  
     
     
         3 . A compound of formula II  
       
         
           
           
               
               
           
         
         wherein  
         R 1  is (C 1 -C 8 )-alkyl, (C 2 -C 4 )-alkenyl or a group of formula A  
           R 3 (OCH 2 CH 2 ) n —  (A)  
         wherein  
         R 3  is hydrogen or (C 1 -C 4 )-alkyl; and  
         n is 1, 2 or 3;  
         R 21 , R 22  and R 23  are each independently hydrogen or halogen; and  
         R 24  is hydrogen, methyl or halogen.  
       
     
     
         4 . A derivative of a compound of formula II according to  claim 3  which derivative is selected from carboxamides, N-substituted carboxamides, N,N-disubstituted carboximides, carboxamidines, N-hydroxy carboxamidines, carboxylic acid hydroxamides, carboxylic acid hydrazides, carbonitriles, carbaldehydes, ketones, isocyanates, carbamates, ureas, N-substituted ureas, N,N-disubstituted ureas, prim., sec. and tert. amines, N-amides, guanidines, aminomethyl, hydroxymethyl, derivatives, and ester derivatives.  
     
     
         5 . A compound of formula IVa or formula IVb  
       
         
           
           
               
               
           
         
         wherein R 21 , R 22 , R 23  are each independently hydrogen or halogen;  
         R 24  is hydrogen, methyl or halogen;  
         R is CN, CHO, CH 2 R 4 , C(O)R 5 , C(O)NHR 6 , C(NH)NH 2 , NHR 7  or C(O)OR 8 ;  
         R 4  is OH or NH 2 ;  
         R 5  is (C 1 -C 6 )-alkyl;  
         R 6  is H, OH, NH 2  or (C 1 -C 6 )-alkyl;  
         R 7  is H or C(NH)NH 2 ; and  
         R 8  is (C 1 -C 6 )-alkyl.