Method for Preparing L-Glufosinate

Abstract

Provided are a method for preparing L-glufosinate and the intermediate compounds of formula (V) and formula (III).

We claim: 
     
         1 . A method for preparing L-glufosinate (I), characterized in that the method comprises the following steps: 
       
         
           
           
               
               
           
         
         a) preparing a compound of Formula (III) from a compound of Formula (II), and 
       
       
         
           
           
               
               
           
         
         b) preparing L-glufosinate from the compound of Formula (III), 
         wherein: 
         X is halogen; 
         Y is —OR 1  or —N(R 2 )(R 3 ); 
         R 1 , R 2  and R 3  are each independently substituted or unsubstituted alkyl having 1-6 carbon atoms, substituted or unsubstituted alkenyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkenyl having 2-6 carbon atoms), substituted or unsubstituted alkynyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkynyl having 2-6 carbon atoms), substituted or unsubstituted cycloalkyl having 3-10 carbon atoms, substituted or unsubstituted aryl having 6-20 carbon atoms, or substituted or unsubstituted heteroaryl having 2-10 carbon atoms, or —Si(R 4 )(R 5 )(R 6 ); 
         R 4 , R 5  and R 6  are each independently substituted or unsubstituted alkyl having 1-6 carbon atoms, or substituted or unsubstituted aryl having 6-20 carbon atoms; and 
         substituents for the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl groups are each independently halogen, carboxyl, amino, nitro, cyano, alkyl having 1-6 carbon atoms, aryl having 6-10 carbon atoms, or cycloalkyl having 3-10 carbon atoms. 
       
     
     
         2 . The method according to  claim 1 , characterized in that the step a) comprises the following step c):
 preparing a compound of Formula (V) by reacting the compound of Formula (II) with a compound of Formula (IV),   
       
         
           
           
               
               
           
         
         wherein: 
         Hal is halogen; 
         X and Y are as defined in  claim 1 ; 
         R 7  is hydrogen, substituted or unsubstituted alkyl having 1-6 carbon atoms, substituted or unsubstituted alkenyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkenyl having 2-6 carbon atoms), or substituted or unsubstituted alkynyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkynyl having 2-6 carbon atoms), and substituents for the alkyl, alkenyl and alkynyl groups are each independently halogen, carboxyl, amino, nitro, cyano, alkyl having 1-6 carbon atoms, aryl having 6-10 carbon atoms, or cycloalkyl having 3-10 carbon atoms. 
       
     
     
         3 . The method according to  claim 2 , characterized in that the step a) comprises a step d) of converting the compound of Formula (V) to the compound of Formula (III), after the step c). 
     
     
         4 . The method according to  claim 1 , characterized in that the Y is —OR 1 , and R 1  is methyl, ethyl, propyl (e.g., n-propyl, isopropyl), butyl (e.g., n-butyl, isobutyl or tert-butyl), amyl, hexyl, benzyl, phenyl or naphthyl, preferably ethyl, n-propyl, isopropyl or n-butyl, and more preferably ethyl. 
     
     
         5 . The method according to  claim 2 , characterized in that the R 7  is methyl, ethyl, propyl, butyl, amyl or hexyl, preferably ethyl. 
     
     
         6 . The method according to  claim 2 , characterized in that in the step c), the reaction temperature is −30° C. to 30° C. 
     
     
         7 . The method according to  claim 2 , characterized in that in the step c), the molar ratio of the compound of Formula (II) to the compound of Formula (IV) is 1:(0.5-10). 
     
     
         8 . The method according to  claim 2 , characterized in that the step c) is performed in the presence of a base. 
     
     
         9 . The method according to  claim 8 , characterized in that the base used in the step c) is an organic base or ammonia. 
     
     
         10 . The method according to  claim 9 , characterized in that in the step c), the organic base is selected from the group consisting of organic amine, pyridine or a pyridine derivative having 1 to 3 substituents attached to one or more carbon atoms in the heterocycle, and piperidine or a piperidine derivative having 1 to 3 substituents attached to one or more carbon atoms in the heterocycle. 
     
     
         11 . The method according to  claim 10 , characterized in that the organic base is selected from the group consisting of triethylamine, piperidine, and pyridine. 
     
     
         12 . The method according to  claim 3 , characterized in that in the step d), the compound of Formula (V) is converted to the compound of Formula (III) at a temperature of 50° C. to 150° C. 
     
     
         13 . The method according to  claim 3 , characterized in that the step c) and the step d) are a one-pot process. 
     
     
         14 . The method according to  claim 1 , characterized in that the step b) is performed by hydrolyzing the compound of Formula (III) in the presence of an acid catalyst. 
     
     
         15 . The method according to  claim 14 , characterized in that the acid catalyst is hydrochloric acid, acetic acid, or a Lewis acid. 
     
     
         16 . The method according to  claim 1 , characterized in that in the step b), the reaction temperature is 20° C. to 200° C., preferably 60° C. to 120° C. or 90° C. to 100° C. 
     
     
         17 . The method according to  claim 1 , characterized in that the L-glufosinate has an enantiomeric excess (ee) value of greater than 50%. 
     
     
         18 . The method according to  claim 17 , characterized in that the L-glufosinate has an ee value of greater than 90%. 
     
     
         19 . A method for preparing L-glufosinate (I), characterized in that the method comprises a reaction of preparing the L-glufosinate (I) from a compound of Formula (III): 
       
         
           
           
               
               
           
         
         wherein Y is as defined in  claim 1 ; 
         preferably, the reaction is performed through hydrolysis in the presence of an acid catalyst, and the acid catalyst is preferably hydrochloric acid, acetic acid, or a Lewis acid; and 
         preferably, the reaction is performed at a temperature of 20° C. to 200° C. 
       
     
     
         20 . A compound, wherein:
 the compound is of Formula (V),   
       
         
           
           
               
               
           
         
         wherein: 
         X is halogen; 
         Y is —OR 1  or —N(R 2 )(R 3 ); 
         R 1 , R 2  and R 3  are each independently substituted or unsubstituted alkyl having 1-6 carbon atoms, substituted or unsubstituted alkenyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkenyl having 2-6 carbon atoms), substituted or unsubstituted alkynyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkynyl having 2-6 carbon atoms), substituted or unsubstituted cycloalkyl having 3-10 carbon atoms, substituted or unsubstituted aryl having 6-20 carbon atoms, or substituted or unsubstituted heteroaryl having 2-10 carbon atoms, or —Si(R 4 )(R 5 )(R 6 ); 
         R 4 , R 5  and R 6  are each independently substituted or unsubstituted alkyl having 1-6 carbon atoms, or substituted or unsubstituted aryl having 6-20 carbon atoms; 
         R 7  is hydrogen, substituted or unsubstituted alkyl having 1-6 carbon atoms, substituted or unsubstituted alkenyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkenyl having 2-6 carbon atoms), or substituted or unsubstituted alkynyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkynyl having 2-6 carbon atoms); 
         substituents for the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl groups are each independently halogen, carboxyl, amino, nitro, cyano, alkyl having 1-6 carbon atoms, aryl having 6-10 carbon atoms, or cycloalkyl having 3-10 carbon atoms; and 
         preferably, the compound of Formula (V) is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         Alternatively, the compound is of Formula (III), 
       
       
         
           
           
               
               
           
         
         wherein: 
         Y is —OR 1  or —N(R 2 )(R 3 ), provided that Y is not —OEt; 
         R 1 , R 2  and R 3  are each independently substituted or unsubstituted alkyl having 1-6 carbon atoms, substituted or unsubstituted alkenyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkenyl having 2-6 carbon atoms), substituted or unsubstituted alkynyl having 1-6 carbon atoms (preferably, substituted or unsubstituted alkynyl having 2-6 carbon atoms), substituted or unsubstituted cycloalkyl having 3-10 carbon atoms, substituted or unsubstituted aryl having 6-20 carbon atoms, or substituted or unsubstituted heteroaryl having 2-10 carbon atoms, or —Si(R 4 )(R 5 )(R 6 ); 
         R 4 , R 5  and R 6  are each independently substituted or unsubstituted alkyl having 1-6 carbon atoms, or substituted or unsubstituted aryl having 6-20 carbon atoms; 
         substituents for the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl groups are each independently halogen, carboxyl, amino, nitro, cyano, alkyl having 1-6 carbon atoms, aryl having 6-10 carbon atoms, or cycloalkyl having 3-10 carbon atoms; and 
         preferably, the compound of Formula (III) is selected from the group consisting of: