Purification process

Abstract

Processes for the depletion of 7-ADCA in mixtures of vinyl-ACA with 7-ADCA via novel salts of vinyl-ACA or via chromatography.

1 . A process for the depletion of 7-ADCA of formula  
       
         
           
           
               
               
           
         
       
       in a mixture of 7-ADCA and vinyl-ACA of formula  
       
         
           
           
               
               
           
         
       
     
     
         2 . A process according to    claim 1   , wherein 
 a) a mixture of a salt of a compound of formula I and a compound of formula II is subjected to crystallization, the crystallised salt is isolated and converted into a compound of formula I, containing less compound of formula II than the mixture of a compound of formula I and formula II, or    b) a mixture of a compound of formula I and a compound of formula II is subjected to chromatography.    
     
     
         3 . A process according to    claim 2   , wherein a mixture of a salt of a compound of formula I and a compound of formula II is a mixture of compounds of formulae  
       
         
           
           
               
               
           
         
       
       wherein X +  denotes a cation, or a compound of formula  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2  and R 3  are the same or different and independently of one another denote hydrogen, alkyl, aryl, aralkyl, or cycloalkyl; or  
 R 1  and R 2  together with the nitrogen atom form a heterocycle and R 3  is as defined above.  
 
     
     
         4 . A process according to    claim 2   , wherein a mixture of a salt of a compound of formula I and a compound of formula II is produced by addition of a salt forming agent to a mixture of a compound of formula I as defined in    claim 1    and a compound of formula II as defined in    claim 1    in a solvent.  
     
     
         5 . A process according to    claim 4   , wherein the salt forming agent is an inorganic base, an inorganic salt, an organic salt or a nitrogen base.  
     
     
         6 . A process according to    claim 5   , wherein the inorganic base is a hydroxide; the inorganic salt is an inorganic alkali salt; the organic salt is an alkali salt of a carboxylic acid; and the nitrogen base is a compound of formula  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2  and R 3  are as defined in    claim 3   .  
     
     
         7 . A compound of formula  
       
         
           
           
               
               
           
         
       
       wherein X +  is as defined in    claim 3   , in crystalline form.  
     
     
         8 . Dicyclohexylammonium salt of 7-amino-3-vinyl-cephalosporanic acid in crystalline form 
 Tert.octylammonium salt of 7-amino-3-vinyl-cephalosporanic acid in crystalline form    N-Benzyl-tert.butylammonium salt of 7-amino -3-vinyl -cephalosporanic acid in crystalline form    2-Ethyl-1-hexylammonium salt of 7-amino-3-vinyl-cephalosporanic acid in crystalline form    Potassium salt of 7-amino-3-vinyl-cephalosporanic acid in crystalline form.    
     
     
         9 . Use of a compound of formula  
       
         
           
           
               
               
           
         
       
       wherein X +  is as defined in    claim 3   , or the use of a process as defined in    claim 1   , in the production of highly active cephalosporins.  
     
     
         10 . Depletion process of 7-ADCA of formula  
       
         
           
           
               
               
           
         
       
       in mixtures of vinyl-ACA of formula  
       
         
           
           
               
               
           
         
       
       with 7-ADCA, characterised in that 
 a) a mixture of vinyl-ACA and 7-ADCA is converted into salts of formula  
                     
  wherein X ⊕  is Li ⊕ , Na ⊕ , K +  or a cation of formula  
                     
  wherein R 1 ′, R 2 ′ and R 3 ′ are the same or different and independently of one another denote hydrogen, (C 1-8 )alkyl, optionally substituted benzyl or phenyl or (C 4-8 )cycloalkyl, or R 1 ′ and R 2 ′ together with the nitrogen form a 5- or 6-membered heterocycle which optionally contains a further one or two hetero atoms, and R 3 ′ is as defined above,  
 by reaction of the mixture of vinyl-ACA and 7-ADCA with a lithium, sodium or potassium base or with an amine of formula  
                     
 wherein R 1 ′, R 2 ′ and R 3 ′ are as defined above, whereby  
 α) the reaction is carried out in a solvent or solvent mixture in which the salts of formulae III and IV have different solubilities, or  
 β) the salts of the compounds of formulae III and IV are suspended in a solvent or solvent mixture, and the solubility product is adjusted,  
 and after isolating the compound of formula III, this is converted using an acid into the compound of formula I having no content or a reduced content of 7-ADCA, or  
 b) a solution of a mixture of vinyl-ACA with 7-ADCA is subjected to chromatography.