Process for producing carbapenem derivative and intermediate crystal therefor

Abstract

An object of the present invention is to provide a carbapenem synthetic intermediate which is advantageous in an industrial process. There are provided a process for producing Compound (I), or a pharmaceutically acceptable salt, or a solvate, or a crystal thereof, comprising reacting Compound (III) and Compound (IV) in the presence of the secondary amine, and a benzyl alcoholated crystal of Compound (I). There are further provided a method of deprotecting Compound (I) with a Pd catalyst, and a crystal of Compound (IV).

1 . A process for producing Compound (I) represented by the formula: 
       
         
           
           
               
               
           
         
         (wherein R 1  and R 2  are as defined below), 
         or a pharmaceutically acceptable salt thereof, or a solvate or a crystal thereof, comprising: 
         reacting Compound (III) represented by the formula: 
       
       
         
           
           
               
               
           
         
         (wherein R is hydrogen or a hydroxyl protecting group; R 1  is a carboxy protecting group; Ph is phenyl) 
         with Compound (IV) represented by the formula: 
       
       
         
           
           
               
               
           
         
         (wherein R 2  is an amino protecting group), 
         or a pharmaceutically acceptable salt thereof in the presence of secondary amine and, optionally, deprotecting the hydroxyl protecting group. 
       
     
     
         2 . The process according to  claim 1 , wherein the secondary amine is diisopropylamine. 
     
     
         3 . The process according to  claim 1 , wherein R 1  is CH 2 CH═CH 2 ; R 2  is COOCH 2 CH═CH 2 . 
     
     
         4 - 18 . (canceled) 
     
     
         19 . The process according to  claim 2 , wherein R 1  is CH 2 CH═CH 2 ; R 2  is COOCH 2 CH═CH 2 .