Process for producing 3-alkoxy-2-amino-6-fluorobicyclo [3.1.0] hexane-2,6-dicarboxylic acid derivative and intermediate thereof

Abstract

A process for producing a 3-alkoxy-2-amino-6-fluoro bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative represented by the formula (I) or a salt thereof, which includes converting a compound represented by the formula (VI) or a salt thereof to the compound represented by the formula (I) or a salt thereof.

1 - 11 . (canceled) 
     
     
         12 . A process for producing a 3-alkoxy-2-amino-6-fluoro bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative represented by the formula (I) or a salt thereof, the process comprising: 
       
         
           
           
               
               
           
         
         (in the formula (I), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure), 
         (A) converting a compound represented by the formula (II) or a salt thereof to a compound represented by the formula (III) or a salt thereof, 
       
       
         
           
           
               
               
           
         
         (in the formula (II), R 3  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group) 
       
       
         
           
           
               
               
           
         
         (in the formula (III), R 4  represents —SiR 41 R 42 R 43  wherein R 41 , R 42 , and R 43 , which may be the same or different from each other, each represent a C 1-6  alkyl group. R 5  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group) 
         (B) converting the compound represented by the formula (III) or a salt thereof to a compound represented by the formula (IV) or a salt thereof, 
       
       
         
           
           
               
               
           
         
         (in the formula (IV), R 6  represents a hydrogen atom, a benzoyl group, a benzoyl group substituted with a halogen atom, or —SiR 61 R 62 R 63  wherein R 61 , R 62 , and R 63 , which may be the same or different from each other, each represent a C 1-6  alkyl group. R 7  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group) 
         (C) converting the compound represented by the formula (IV) or a salt thereof to a compound represented by the formula (V) or a salt thereof, 
       
       
         
           
           
               
               
           
         
         (in the formula (V), R 1  and R 2  are as defined in the above and R 8  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group) 
         (H) converting the compound represented by the formula (V) or a salt thereof to a compound represented by the formula (IX) or a salt thereof, 
       
       
         
           
           
               
               
           
         
         (in the formula (IX), R 1  and R 2  are as defined in the above and R 12  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group), and 
         (I) converting the compound represented by the formula (IX) or a salt thereof to the compound represented by the formula (I) or a salt thereof. 
       
     
     
         13 . A compound represented by the formula (IV) or a salt thereof 
       
         
           
           
               
               
           
         
         (in the formula (IV), R 6  represents a hydrogen atom, a benzoyl group, a benzoyl group substituted with a halogen atom, or —SiR 61 R 62 R 63  wherein R 61 , R 62 , and R 63 , which may be the same or different from each other, each represent a C 1-6  alkyl group. R 7  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group). 
       
     
     
         14 . A compound represented by the formula (V) or a salt thereof 
       
         
           
           
               
               
           
         
       
       (in the formula (V), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure. R 8  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group). 
     
     
         15 . A compound represented by the formula (VI) or a salt thereof 
       
         
           
           
               
               
           
         
         (in the formula (VI), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure. R 9  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group). 
       
     
     
         16 . A compound represented by the formula (VIII) or a salt thereof 
       
         
           
           
               
               
           
         
         (in the formula (VIII), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure. R 13  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group). 
       
     
     
         17 . A compound represented by the formula (VII) or a salt thereof 
       
         
           
           
               
               
           
         
         (in the formula (VII), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure. R 10  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group. R 11  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group, with the proviso that, R 10  and R 11  do not simultaneously represent a hydroxyl group and do not simultaneously represent a C 1-6  alkoxy group. When any one of R 10  and R 11  is a hydroxyl group, the other is not a C 1-6  alkoxy group). 
       
     
     
         18 . A compound represented by the formula (IX) or a salt thereof 
       
         
           
           
               
               
           
         
         (in the formula (IX), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure. R 12  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group). 
       
     
     
         19 . A compound represented by the formula (X) or a salt thereof 
       
         
           
           
               
               
           
         
         (in the formula (X), R 1  and R 2 , which may be the same or different from each other, each represent a hydrogen atom, a C 1-10  alkyl group, a C 2-10  alkenyl group, a phenyl group, a naphthyl group, a naphthyl group substituted with 1 to 7 halogen atoms, a heteroaromatic group, or a phenyl group substituted with 1 to 5 substituent groups selected from a group consisting of a halogen atom, a C 1-10  alkyl group, a C 1-10  alkoxy group, a trifluoro methyl group, a phenyl group, a hydroxy carbonyl group, an amino group, a nitro group, a cyano group, and a phenoxy group. Further, R 1  and R 2  may bind to each other to form a cyclic structure. R 14  represents a C 1-6  alkoxy group, an amino group, or a hydroxyl group).