Process for Manufacturing Substituted 5-Methoxymethylpyridine-2,3-Dicarboxylic Acid Derivatives

Abstract

A process for manufacturing a 2,3-disubstituted-5-methoxymethylpyridine of formula (I), where Z is H or halogen; Z 1 is H, halogen, CN or NO 2 ; Y 2 is OM, and M is an alkali metal or an alkaline earth metal, comprises the step of: (i) reacting a compound of formula (II) where Q is a tertiary aliphatic or cyclic, saturated, partially unsaturated or aromatic amine; Z is H or halogen; Z 1 is H, halogen, CN or NO 2 ; Y 1 and Y 2 are each independently OR 1 , NR 1 R 2 , or when taken together Y 1 Y 2 is —O—, —S— or —NR 3 —; R 1 and R 2 are each independently H, C 1 -C 4 alkyl optionally substituted with C 1 -C 1 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; R 3 is H or C 1 -C 4 alkyl, in a methanol/H 2 O mixture, comprising at least 20% by weight H 2 O (based on the sum of water and bromide (II)), with a base comprising MOCH 3 and/or MOH, where M is alkali metal or alkaline earth metal, under pressure in a closed vessel at a temperature of from 75 to 110° C. Compounds of formula (I) are useful intermediates in the synthesis of herbicidal imidazolinones, like imazamox.

1 - 17 . (canceled) 
     
     
         18 . A process for manufacturing a compound of formula (I), 
       
         
           
           
               
               
           
         
         wherein 
         Z is H or halogen; 
         Z 1  is H, halogen, CN or NO 2 ; 
         Y is OM, and 
         M is an alkali metal or an alkaline earth metal, 
         comprising 
         reacting a compound of formula (II) 
       
       
         
           
           
               
               
           
         
         wherein 
         Q is a tertiary aliphatic or cyclic, saturated, partially unsaturated or aromatic amine; 
         Z is H or halogen; 
         Z 1  is H, halogen, CN or NO 2 ; 
         Y 1  and Y 2  are each independently OR 1 , NR 1 R 2 , or when taken together Y 1 Y 2  is —O—, —S— or —NR 3 —; 
         R 1  and R 2  are each independently H, C 1 -C 4  alkyl optionally substituted with C 1 -C 4  alkoxy, or phenyl optionally substituted with one to three C 1 -C 4  alkyl groups, C 1 -C 4  alkoxy groups, or halogen atoms; 
         R 3  is H or C 1 -C 4  alkyl, 
         in a methanol/H 2 O mixture, comprising at least 20% by weight H 2 O, based on the sum of water and the compound of formula (II), 
         with a base comprising MOCH 3  and/or MOH, where M is alkali metal or alkaline earth metal, under pressure in a closed vessel at a temperature of from 75 to 110° C. 
       
     
     
         19 . The process of  claim 18 , further comprising:
 (i-1) reacting a compound of formula (IV),   
       
         
           
           
               
               
           
         
         with bromine in the presence of a radical initiator in a solvent mixture comprising an aqueous phase and an organic phase, wherein the organic phase comprises a solvent selected from the group consisting of 1,2-dichloroethane, chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene and tetrachloromethane, and where the pH-value of the aqueous phase is from 3 to <8, 
         to obtain a compound of formula (V), 
       
       
         
           
           
               
               
           
         
         and 
         (i-2) reacting the compound of formula (V) with a tertiary amine Q in a solvent at a temperature range of 0 to 100° C. to the compound of formula (II), and 
         (i-3) reacting the compound of formula (II) in a methanol/H 2 O mixture, with a base comprising MOCH 3  and MOH, where M is alkali metal, under pressure in a closed vessel at a temperature of from 75 to 110° C. 
       
     
     
         20 . The process of  claim 18 , wherein the compound of formula (II) is the compound (IIa) 
       
         
           
           
               
               
           
         
       
     
     
         21 . The process of  claim 18 , wherein the ratio of methanol to compound of formula (II) is in the range of from 0.5-25:1. 
     
     
         22 . The process of  claim 18 , wherein the base is a mixture of MeOM and MOH. 
     
     
         23 . The process of  claim 18 , wherein the base is MeOM. 
     
     
         24 . The process of  claim 22 , wherein the molar ratio of MeOM to compound of formula (II) is in the range of from 1-10:1. 
     
     
         25 . The process of  claim 23 , wherein the molar ratio of MeOM to compound of formula (II) is in the range of from 1-10:1. 
     
     
         26 . The process of  claim 18 , wherein the base is MOH. 
     
     
         27 . The process of  claim 22 , wherein the molar ratio of MOH to compound of formula (II) is in the range of from 0.5-10:1. 
     
     
         28 . The process of  claim 26 , wherein the molar ratio of MOH to compound of formula (II) is in the range of from 0.5-10:1. 
     
     
         29 . The process of  claim 18 , wherein the molar ratio of total amount of base added to the compound of formula (II) is 3-7:1. 
     
     
         30 . The process of  claim 18 , wherein the reaction temperature is in the range of from about 75 to 110° C. 
     
     
         31 . The process of  claim 18 , which is carried out at a pressure of 1.01 to 5.00 bar. 
     
     
         32 . A process for preparing a compound of formula (III), 
       
         
           
           
               
               
           
         
         wherein 
         Z is H or halogen; 
         Z 1  is H, halogen, CN or NO 2 ; 
         R 4  is C 1 -C 4  alkyl; 
         R 5  is C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl or R 4  and R 5 , when taken together with the atom to which they are attached, represent a C 3 -C 6  cycloalkyl group optionally substituted with methyl, and 
         R 6  is hydrogen; a group of the formula —N═C (lower alkyl) 2 ; C 1 -C 12  alkyl optionally substituted with one of the following groups: C 1 -C 3  alkoxy, halogen, hydroxyl, C 3 -C 6 -cycloalkyl, benzyloxy, furyl, phenyl, halophenyl, lower alkylphenyl, lower alkoxyphenyl, nitrophenyl, carboxyl, lower alkoxycarbonyl, cyano or tri lower alkylammonium; C 3 -C 12  alkenyl optionally substituted with one of the following groups: C 1 -C 3  alkoxy, phenyl, halogen or lower alkoxycarbonyl or with two C 1 -C 3  alkoxy groups or two halogen groups; C 3 -C 6  cycloalkyl optionally substituted with one or two C 1 -C 3  alkyl groups; or 
         a cation; 
         comprising: 
         (i) preparing the compound of formula (I) according to  claim 18 ; 
         (ii) converting the compound of formula (I) into the compound of formula (III). 
       
     
     
         33 . The process of  claim 32 , further comprising:
 (i) preparating the compound (I), where Y is OH,   (ii-1) converting the compound (I) to the compound of formula (VI),   
       
         
           
           
               
               
           
         
         wherein 
         Z is H or halogen; 
         Z 1  is H, halogen, CN or NO 2 ; 
         (ii-2) reacting the compound of formula (VI) with a compound of formula (VII),
   H 2 N—CR 4 R 5 —CONH 2   (VII),
 
 
         wherein 
         R 4  is C 1 -C 4  alkyl; 
         R 5  is C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl or R 4  and R 5 , when taken together with the atom to which they are attached, represent a C 3 -C 6  cycloalkyl group optionally substituted with methyl, 
         to yield a compound of formula (VIII), 
       
       
         
           
           
               
               
           
         
         and 
         (ii-3) condensing the compound of formula (VIII) to yield the compound of formula (III). 
       
     
     
         34 . The process of  claim 32 , further comprising:
 preparing the compound (I), where Y is OH;   (ii-1) converting the compound of formula (I) to the compound of formula (VI),   
       
         
           
           
               
               
           
         
         (ii-2) reacting the compound of formula (VI) with a compound of formula (IX),
   H 2 N—CR 4 R 5 —CN  (IX);
 
 
         to obtain a compound of formula (X), 
       
       
         
           
           
               
               
           
         
         (ii-3) hydrolyzing the compound of formula (X) to yield a compound of formula (VIII), 
       
       
         
           
           
               
               
           
         
         and 
         (ii-4) condensing the compound of formula (VIII) to yield the compound of formula (III).