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

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 converting a compound represented by the formula (VI) or a salt thereof to the compound represented by the formula (I) or a salt thereof

• (in the formula (I), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure),
• (in the formula (VI), R1 and R2 are as defined in the above and R9 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).

A compound represented by the formula (IV) or a salt thereof

• (in the formula (IV), R6 represents a hydrogen atom, a benzoyl group, a benzoyl group substituted with a halogen atom, or —SiR61R62R63 wherein R61, R62, and R63, which may be the same or different from each other, each represent a C1-6 alkyl group. R7 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).

A compound represented by the formula (V) or a salt thereof

• (in the formula (V), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure. R8 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).

A compound represented by the formula (VI) or a salt thereof

• (in the formula (VI), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure. R9 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).

A compound represented by the formula (VIII) or a salt thereof

• (in the formula (VIII), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure. R13 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).

A compound represented by the formula (VII) or a salt thereof

• (in the formula (VII), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure. R10 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group. R11 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group, with the proviso that, R10 and R11 do not simultaneously represent a hydroxyl group and do not simultaneously represent a C1-6 alkoxy group. When any one of R10 and R11 is a hydroxyl group, the other is not a C1-6 alkoxy group).

A compound represented by the formula (IX) or a salt thereof

• (in the formula (IX), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure. R12 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).

A compound represented by the formula (X) or a salt thereof

• (in the formula (X), R1 and R2, which may be the same or different from each other, each represent a hydrogen atom, a C1-10 alkyl group, a C2-10 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 C1-10 alkyl group, a C1-10 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, R1 and R2 may bind to each other to form a cyclic structure. R14 represents a C1-6 alkoxy group, an amino group, or a hydroxyl group).