Preparation of chiral amino-nitriles

Abstract

A process and intermediates for producing 3-amino nitrites. The process involves resolving an enantiomeric mixture of chiral 3-amino nitrites in the presence of a chiral acid in a solvent system to produce a chiral 3-amino nitrile salt. The process may further comprise a recrystalizing step, wherein an enantiomerically enriched 3-amino nitrile salt is produced. The process may further comprise a salt exchanging step, wherein another acid is added to the chiral 3-amino nitrile salt or the enantiomerically enriched 3-amino nitrile salt to produce another 3-amino nitrile salt.

What is claimed is:  
     
         1 . A process for producing 3-amino nitrile compounds comprising the steps of: 
 providing an enantiomeric mixture of chiral 3-amino nitrites; and    resolving said enantiomeric mixture of chiral 3-amino nitrites in the presence of a chiral acid in a solvent system to produce a chiral 3-amino nitrile salt.    
     
     
         2 . The process of  claim 1  wherein said enantiomeric mixture comprises a racemic mixture.  
     
     
         3 . The process of  claim 2  wherein said racemic mixture comprises (R)-3-aminopentanenitrile and (S)-3-aminopentanenitrile.  
     
     
         4 . The process of  claim 1  wherein said chiral acid comprises at least one of dibenzoyl-(L)-tartaric acid, dibenzoyl-(D)-tartaric acid, and di-p-toluoyl-(D)-tartaric acid.  
     
     
         5 . The process of  claim 4  wherein said dibenzoyl-(L)-tartaric acid comprises at least one of dibenzoyl-(L)-tartaric acid monohydrate, and dibenzoyl-(L)-tartaric acid anhydrous.  
     
     
         6 . The process of  claim 1  wherein said chiral acid comprises dibenzoyl-(L)-tartaric acid and said chiral 3-amino nitrile salt comprises (R)-3-aminopentanenitrile dibenzoyl-(L)-tartrate salt of the structure:  
       
         
           
           
               
               
           
         
       
     
     
         7 . The process of  claim 1  wherein said solvent system comprises at least one of ethyl acetate, toluene, acetonitrile, and water.  
     
     
         8 . The process of  claim 1  wherein said chiral 3-amino nitrile salt has an optical purity of at least about 45% ee.  
     
     
         9 . The process of  claim 8  wherein said chiral 3-amino nitrile salt has an optical purity of between about 65% ee and about 95% ee.  
     
     
         10 . The process of  claim 1  further comprising the step of: 
 recovering said chiral 3-amino nitrile salt.  
 
     
     
         11 . The process of  claim 10  further comprising the step of: 
 recrystalizing said recovered chiral 3-amino nitrile salt in a recrystalizing solvent to form an enantiomerically enriched 3-amino nitrile salt having an optical purity of at least about 89% ee.  
 
     
     
         12 . The process of  claim 11  wherein said enantiomerically enriched 3-amino nitrile salt comprises (R)-3-aminopentanenitrile dibenzoyl-(L)-tartrate salt of the structure:  
       
         
           
           
               
               
           
         
       
     
     
         13 . The process of  claim 11  wherein said recrystalizing solvent comprises at least one of ethyl acetate, methyl ethyl ketone, isopropyl alcohol/water, acetonitrile, ethyl alcohol, methyl tert-butyl ether, dichloromethane/water, and tetrahydrofuran.  
     
     
         14 . The process of  claim 11  further comprising the step of: 
 recovering said enantiomerically enriched 3-amino nitrite salt.  
 
     
     
         15 . The process of  claim 14  further comprising the step of: 
 adding another acid to said enantiomerically enriched 3-amino nitrite salt to form another 3-amino nitrite salt.  
 
     
     
         16 . The process of  claim 15  further comprising the step of: 
 recovering said other 3-amino nitrite salt.  
 
     
     
         17 . The process of  claim 15  wherein said other acid comprises at least one of methanesulfonic acid and hydrochloric acid.  
     
     
         18 . The process of  claim 15  wherein said other 3-amino nitrile salt icomprises at least one of (R)-3-aminopentanenitrile methanesulfonic acid salt of the structure:  
       
         
           
           
               
               
           
         
         and (R)-3-aminopentanenitrile hydrochloric acid salt of the structure:  
         
           
             
             
                 
                 
             
           
         
       
     
     
         19 . The process of  claim 10  further comprising the step of: 
 adding another acid to said chiral 3-amino nitrile salt to form another 3-amino nitrile salt.  
 
     
     
         20 . The process of  claim 19  further comprising the step of: 
 recovering said other 3-amino nitrile salt.  
 
     
     
         21 . The process of  claim 19  wherein said other acid comprises at least one of methanesulfonic acid and hydrochloric acid.  
     
     
         22 . The process of  claim 19  wherein said other 3-amino nitrile salt comprises at least one of (R)-3-aminopentanenitrile methanesulfonic acid salt of the structure:  
       
         
           
           
               
               
           
         
       
       and (R)-3-aminopentanenitrile hydrochloric acid salt of the structure:  
       
         
           
           
               
               
           
         
       
     
     
         23 . The chiral 3-amino nitrile salt produced by the process of  claim 10 .  
     
     
         24 . The enantiomerically enriched 3-amino nitrile salt produced by the process of  claim 11 .  
     
     
         25 . The (R)-3-aminopentanenitrile methanesulfonic acid salt produced by the process of  claim 18 .  
     
     
         26 . The (R)-3-aminopentanenitrile methanesulfonic acid salt produced by the process of  claim 22 .  
     
     
         27 . The (R)-3-aminopentanenitrile hydrochloric acid salt produced by the process of  claim 18 .  
     
     
         28 . The (R)-3-aminopentanenitrile hydrochloric acid salt produced by the process of  claim 22 .  
     
     
         29 . An (R)-3-aminopentanenitrile dibenzoyl-(L)-tartrate salt having the following general structure:  
       
         
           
           
               
               
           
         
       
     
     
         30 . An (R)-3-aminopentanenitrile-dibenzoyl-(D)-tartrate salt having the following general structure:  
       
         
           
           
               
               
           
         
       
     
     
         31 . A process for producing 3-amino nitrile compounds comprising the steps of: 
 providing an (R)-3-aminopentanenitrile dibenzoyl-(L)-tartrate salt having the following general structure:                           ; and    adding another acid thereto to form another (R)-3-aminopentanenitrile salt.    
     
     
         32 . The process of  claim 31  wherein said another acid comprises at least one of methanesulfonic acid and hydrochloric acid.  
     
     
         33 . The process of  claim 31  wherein said (R)-3-aminopentanenitrile salt comprises at least one of (R)-3-aminopentanenitrile methanesulfonic acid salt of the structure:  
       
         
           
           
               
               
           
         
       
       and (R)-3-aminopentanenitrile hydrochloric acid salt of the structure:  
       
         
           
           
               
               
           
         
       
     
     
         34 . A process for producing 3-amino nitrile compounds comprising the steps of: 
 providing an (R)-3-aminopentanenitrile dibenzoyl-(D)-tartrate salt having the following general structure:                           ; and    adding another acid thereto to form another (R)-3-aminopentanenitrile salt.    
     
     
         35 . The process of  claim 34  wherein said other acid comprises at least one of methanesulfonic acid and hydrochloric acid.  
     
     
         36 . The process of  claim 34  wherein (R)-3-aminopentanenitrile salt comprises at least one of (R)-3-aminopentanenitrile methanesulfonic acid salt of the structure:  
       
         
           
           
               
               
           
         
       
       and (R)-3-aminopentanenitrile hydrochloric acid salt of the structure: