Process for the preparation of beta-lactam antibiotic

Abstract

The present invention provides a novel process for the preparation of the meropenem trihydrate of formula (I).

1 . An improved process for preparation of compound of formula (V), which comprises the steps of: 
       
         
           
           
               
               
           
         
         wherein PNB represents p-nitrobenzyl and PNZ represents p-nitrobenzyloxycarbonyl 
         i) reacting the activated compound of formula (III) with mercaptan of formula (IV) in the presence or absence of base in a water-miscible organic solvent to yield compound of formula (V); 
       
       
         
           
           
               
               
           
         
         ii) quenching the reaction mass from step (i) in water in the presence or absence of buffer; 
         iii) optionally adjusting the pH of step (ii) mass to 3.0 to 5.0; and 
         iv) filtering the compound of formula (V). 
       
     
     
         2 . The process as claimed in  claim 1 , wherein the base used in step (i) is selected from organic amines selected from group comprising diisopropylamine, diisopropylethylamine, triethylamine, pyridine, 4-dimethylaminopyridine, tetramethylguanidine (TMG) or mixtures thereof. 
     
     
         3 . The process as claimed in  claim 1 , wherein water-miscible organic solvent used in step (i) is selected from tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidinone, N-ethylpyrrolidinone, N-methylpiperidinone, acetonitrile, propionitrile, acetone, ethanol, methanol, isopropyl alcohol, 1-propanol, methyl ethyl ketone, DMSO or mixtures thereof. 
     
     
         4 . The process as claimed in  claim 3 , wherein water-miscible organic solvent is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidinone; preferably N,N-dimethylformamide. 
     
     
         5 . The process as claimed in  claim 1 , wherein the buffer used in step (ii) is selected from dipotassium hydrogen orthophosphate or potassium dihydrogen orthophosphate. 
     
     
         6 . A process as claimed in  claim 1 , further comprising converting compound of formula (V) into Meropenem or its hydrate by deprotection.