Process for manufacture of fosinopril sodium

Abstract

The present invention discloses a process for the synthesis of fosinopril as a single desired isomer of high purity in two steps comprising of (a) preparation of fosinopril as a mixture of four diastereomers and (b) separation of the desired isomer from the mixture through formation of alkali metal salts followed by crystallisation.

1 - 45 . (canceled)  
   
   
       46 . A crystalline fosinopril sodium intermediate having the following formula (III A)  
     
       
         
         
             
             
         
       
     
   
   
       47 - 53 . (canceled)  
   
   
       54 . The intermediate of formula (III A) according to  claim 46 , which has the X-ray (powder) diffraction pattern  
     
       
         
               
               
               
             
                   
               
                   
               
                 □ 
                 d 
                 I/I 1   
               
                   
               
                   
               
               
               
               
             
                  4.3000 
                 20.53270  
                 14 
               
                  4.6761 
                 18.88206  
                 65 
               
                  4.9800 
                 17.73046  
                 16 
               
                  6.9383 
                 12.72990  
                 4 
               
                  9.0000 
                 9.81785 
                 18 
               
                  9.3400 
                 9.46121 
                 19 
               
                 10.2591 
                 8.61556 
                 8 
               
                 11.1843 
                 7.90485 
                 17 
               
                 13.5200 
                 6.54401 
                 14 
               
                 13.8600 
                 6.38423 
                 19 
               
                 14.3200 
                 6.18017 
                 9 
               
                 14.9000 
                 5.94088 
                 3 
               
                 15.3246 
                 5.77722 
                 99 
               
                 15.9203 
                 5.56236 
                 39 
               
                 16.6550 
                 5.31861 
                 8 
               
                 17.3600 
                 5.10417 
                 6 
               
                 17.8400 
                 4.96791 
                 23 
               
                 18.3005 
                 4.84392 
                 32 
               
                 19.2117 
                 4.61618 
                 33 
               
                 19.8200 
                 4.47586 
                 7 
               
                 20.1837 
                 4.39602 
                 45 
               
                 20.6800 
                 4.29163 
                 26 
               
                 21.0400 
                 4.21900 
                 17 
               
                 21.6800 
                 4.09588 
                 6 
               
                 21.9943 
                 4.03805 
                 26 
               
                 22.5400 
                 3.94151 
                 26 
               
                 22.8624 
                 3.88665 
                 100 
               
                 23.2802 
                 3.81784 
                 82 
               
                 23.8800 
                 3.72328 
                 4 
               
                 24.2400 
                 3.66880 
                 21 
               
                 24.5200 
                 3.62753 
                 13 
               
                 25.0400 
                 3.55337 
                 27 
               
                 25.4000 
                 3.50381 
                 18 
               
                 25.7800 
                 3.45302 
                 31 
               
                 26.3983 
                 3.37353 
                 13 
               
                 26.7986 
                 3.32404 
                 11 
               
                 27.5286 
                 3.23753 
                 6 
               
                 27.9055 
                 3.19465 
                 14 
               
                 28.2600 
                 3.15538 
                 9 
               
                 28.8506 
                 3.09211 
                 20 
               
                 29.3015 
                 3.04555 
                 5 
               
                 30.0261 
                 2.97368 
                 7 
               
                 30.8493 
                 2.89618 
                 49 
               
                 31.1800 
                 2.86621 
                 5 
               
                 31.5400 
                 2.83432 
                 4 
               
                 31.7930 
                 2.81234 
                 19 
               
                 33.2926 
                 2.68901 
                 44 
               
                 34.0710 
                 2.62933 
                 4 
               
                 34.4622 
                 2.60037 
                 11 
               
                 35.3308 
                 2.53841 
                 17 
               
                 36.1300 
                 2.48407 
                 10 
               
                 37.7758 
                 2.37954 
                 27 
               
                 38.3196 
                 2.34702 
                 5 
               
                 38.5848 
                 2.33149 
                 4 
               
                 39.3575 
                 2.28748 
                 9 
               
                 39.8263 
                 2.26163 
                 10 
               
                 40.5967 
                 2.22047 
                 13 
               
                 41.1000 
                 2.19443 
                 3 
               
                 42.3183 
                 2.13403 
                 8 
               
                 43.7725 
                 2.06645 
                 8 
               
                 43.9800 
                 2.05718 
                 4 
               
                 45.1650 
                 2.00592 
                 3 
               
                 45.5060 
                 1.99168 
                 4 
               
                 46.3200 
                 1.95856 
                 4 
               
                 46.5200 
                 1.95060 
                 4 
               
                 47.4679 
                 1.91384 
                 3