Fluorine-containing isoxazole compound and method for producing same

Abstract

The present invention relates to a fluorine-containing isoxazole compound represented by general formula (A). (In general formula (A), R represents a hydrogen atom or a substituted or unsubstituted C1-12 hydrocarbon group, X represents a halogen atom, -OA1, -O-NA1A2, -NA1A2, -NA1(OA2), -NA3-NA1A2, -NA4, or a heterocycle, A1, A2, and A3 each independently represent a substituted or unsubstituted C1-12 hydrocarbon group or a heterocycle, A4 represents an alkylene group represented by =CnH2n, n is an integer of 1-20, and Y1 and Y2 each independently represent N or O and are different from each other.)

Description

Fluorine-containing isoxazole compound and method for producing the same

[0001] The present invention relates to a fluorine-containing isoxazole compound and a method for producing the same.

[0002] Compounds containing an isoxazole ring or its tautomer, an isoxazolone ring, are known to have various pharmacological effects, including natural products such as ibotenic acid and muscimol. Examples of pharmaceuticals include β-lactam antibiotics such as oxacillin and flucloxacillin, sulfonamide antibiotics such as sulfafurazole and sulfamethoxazole, oxazolidinone antibiotics such as posizolid, antirheumatic drugs such as leflunomide and valdecoxib, liver disease treatment drug such as tropifexor, anticancer drug such as tivozanib, antiviral drug such as pleconaril, antidepressant drug such as isocarboxazid, diabetes treatment drug such as glisoxepide, and endometriosis treatment drug such as danazol. Further, examples of pesticides include isoxathion as an insecticide, isoxaben as a herbicide, and the like.

[0003] Given the wide range of pharmacological actions of isoxazoles, there has been recent interest in introducing heteroatom substituents (substituents having a heteroatom) into positions 3 and / or 5. Specifically, Non-Patent Document 1 reports that compounds having an isoxazole ring substituted with a methoxy group at position 3 and a 1-tetrazolyl group at position 5 have cholinesterase inhibitory activity and are therefore being studied as therapeutic agents for Alzheimer's disease.

[0004] Furthermore, the pharmacological effects of compounds having a trifluoromethyl group at the 4-position of the isoxazole ring have also attracted interest. Specifically, Non-Patent Document 2 reports that such compounds have agonistic activity for the sphingosine-1-phosphate receptor S1P1 and are therefore being studied as therapeutic agents for autoimmune diseases.

[0005] From this viewpoint, it is desirable to develop fluorine-containing isoxazole compounds which not only have heteroatom substituents at the 3- and / or 5-positions of the isoxazole ring but also have a trifluoromethyl group at the 4-position of the isoxazole ring, in the hope of finding usefulness as therapeutic agents for various diseases.

[0006] New Journal of Chemistry, 2015, Vol. 39, pp. 2028-2041 Bioorganic & Medicinal Chemistry Letters, 2016, Vol. 26, pp. 2470-2474

[0007] Therefore, the present inventors discovered that by reacting specific raw materials, it is possible to construct a structure having a trifluoromethyl group at the 4-position on the isoxazole ring and substituted with a heteroatom substituent at the 3- and / or 5-position, and thus completed the present invention.

[0008] The present invention provides a novel fluorine-containing isoxazole compound having a trifluoromethyl group at the 4-position on the isoxazolone ring and a heteroatom substituent at the 3-position and / or the 5-position, and a production method that enables the simple production of the fluorine-containing isoxazole compound.

[0009] The fluorine-containing isoxazole compound according to this embodiment is represented by the following general formula (A). (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA ３ -NA １ A ２ , -NA４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.

[0010] The method for producing a fluorine-containing isoxazole compound according to this embodiment includes the steps of: (I) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with hydroxylamine or a salt thereof, and, optionally, a compound represented by the following general formula (5) or a salt thereof, or (II) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with an amine salt or an amine compound, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by the following general formula (A): (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎn is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.

[0011] Provided are novel fluorine-containing isoxazole compounds having a trifluoromethyl group at the 4-position on the isoxazolone ring and a heteroatom substituent at the 3- and / or 5-position, and a production method that enables the easy production of the fluorine-containing isoxazole compounds.

[0012] Hereinafter, embodiments of the present invention will be described in detail. However, the scope of the present invention is not limited to the specific examples described below. Furthermore, the heteroatom substituent is a substituent having a heteroatom, and refers to a functional group containing at least one heteroatom selected from the group consisting of a nitrogen atom (N), a sulfur atom (S), and an oxygen atom (O).

[0013] (Fluorine-Containing Isoxazole Compound) The fluorine-containing isoxazole compound of the present embodiment is represented by the following general formula (A), and has a trifluoromethyl group at the 4-position on the isoxazole ring and a heteroatom substituent at the 3-position and / or 5-position.

[0014] (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎn is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.

[0015] Y １ N, Y ２ When R is O and R is a hydrogen atom, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (1):

[0016] (In the above general formula (1), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, A １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0017] Y １ N, Y ２ When R is O and R is a hydrocarbon group having 1 to 12 carbon atoms, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (2):

[0018] (In the above general formula (2), R represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0019] Y １ O, Y ２ When R is N and R is a hydrogen atom, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (3).

[0020] (In the above general formula (3), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0021] Y １ O, Y ２ When R is N and R is a hydrocarbon group having 1 to 12 carbon atoms, the fluorine-containing isoxazole compound represented by general formula (A) is represented by the following general formula (4):

[0022] (In the above general formula (4), R' represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA１ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0023] When R and R' are substituted or unsubstituted hydrocarbon groups having 1 to 12 carbon atoms, they are not particularly limited as long as they are hydrocarbon groups consisting of carbon atoms and hydrogen atoms having 1 to 12 carbon atoms, and examples thereof include chain hydrocarbon groups, aromatic hydrocarbon groups, and alicyclic hydrocarbon groups. The chain hydrocarbon groups are not particularly limited as long as they have a total of 1 to 12 carbon atoms, and may be linear or branched chain hydrocarbon groups, or may be substituted or unsubstituted chain hydrocarbon groups. When R and R' are aromatic hydrocarbon groups, they are not particularly limited as long as they have a total of 6 to 12 carbon atoms, and may be substituted or unsubstituted aromatic hydrocarbon groups. The aromatic hydrocarbon groups may also have a fused polycyclic structure. When R and R' are alicyclic hydrocarbon groups, they are not particularly limited as long as they have a total of 3 to 12 carbon atoms, and may be substituted or unsubstituted alicyclic hydrocarbon groups. The alicyclic hydrocarbon groups may also have a bridged ring structure.

[0024] Examples of the chain hydrocarbon group include alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl; alkenyl groups such as ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, and dodecenyl; and alkynyl groups such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, and dodecynyl.

[0025] Examples of the aromatic hydrocarbon group include a phenyl group and a naphthyl group.

[0026] Alicyclic hydrocarbon groups include saturated or unsaturated cyclic hydrocarbon groups, and examples of cyclic hydrocarbon groups include a cyclopropyl group, a cyclobutyl group, a cyclohexyl group, a cyclopentyl group, an adamantyl group, and a norbornyl group.

[0027] When the chain hydrocarbon group has a substituent, one of the hydrogen atoms of the chain hydrocarbon group may be substituted with an alkoxyl group or an aralkyl group. The alkoxyl group is preferably an alkoxyl group having 1 to 6 carbon atoms, such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, an n-pentoxy group, or an n-hexyloxy group. The aralkyl group is preferably an alkyl group having 1 to 6 carbon atoms substituted with an aryl group, such as a benzyl group, a phenylethyl group, a phenylpropyl group, or a naphthylmethyl group.

[0028] When the aromatic hydrocarbon group and the alicyclic hydrocarbon group have a substituent, examples of the substituent include the above-mentioned alkyl groups and alkoxy groups having 1 to 6 carbon atoms.

[0029] In X, the halogen atom is F, Cl, Br or I, and is preferably F or Cl.

[0030] In X, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ) and -NA ３ -NA １ A ２ A included in １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocyclic ring having 1 to 12 carbon atoms. １ A ２ , -NA １ A ２ , -NA １ (OA ２ ) or -NA ３ -NA １ A ２ If A １ , A ２ and A ３ may be the same or different. １ , A ２ and A ３ represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, A １ , A ２ and A ３ is the same as the hydrocarbon group having 1 to 12 carbon atoms defined for R and R' above, and can be, for example, a hydrocarbon group having 1 to 12 carbon atoms among the above R and R'. The hydrocarbon group having 1 to 12 carbon atoms is preferably a chain hydrocarbon group having 1 to 12 carbon atoms, more preferably a chain hydrocarbon group having 1 to 10 carbon atoms, still more preferably an alkyl group having 1 to 10 carbon atoms, and particularly preferably an alkyl group having 1 to 4 carbon atoms.

[0031] In X, the heterocycle is an optionally substituted monocyclic, bicyclic, or polycyclic heterocycle containing at least one heteroatom selected from the group consisting of a nitrogen atom (N), a sulfur atom (S), and an oxygen atom (O) as a ring atom. The heterocyclic group may have multiple heteroatoms, which may be the same or different. Each heterocycle preferably contains at least one nitrogen atom as a heteroatom in its skeleton. One of the heteroatoms contained in the heterocyclic group, preferably N, is directly bonded to the isoxazole ring of the fluorine-containing isoxazole compound and is substituted on the isoxazole ring as a heteroatom substituent. The heterocycle may be a fused ring, an alicyclic heterocycle, an aromatic heterocycle, or a combination thereof.

[0032] The monocyclic heterocycle is preferably a 3- to 12-membered ring, and more preferably a 5- to 9-membered ring. When the heterocycle is a monocyclic heterocycle, it may contain up to five heteroatoms. Each heteroatom is independently selected from O, S, and N, and it is preferred that at least one of the heteroatoms is N. Examples of monocyclic heterocycles include pyrrolidine, pyrroline, pyrrole, pyrazolidine, imidazolidine, pyrazoline, imidazoline, imidazole, pyrazole, triazole, tetrazole, (iso)oxazole, (iso)oxadiazole, (iso)thiazole, thiadiazole, pyridine, pyrrolidine, piperidine, piperazine, pyridazine, pyrimidine, pyrazine, triazine, thienopyridine, piperazinone, morpholine, thiomorpholine, thiomorpholine dioxide, oxazine, thiazine, azocane, azocine, azonane, azonine, and derivatives thereof.

[0033] The bicyclic heterocycle is preferably a 7- to 14-membered ring, and more preferably an 8- to 10-membered ring. The bicyclic heterocycle may also contain a spiro ring. When the heterocycle is a bicyclic heterocycle, it may contain up to 10 heteroatoms. Each heteroatom is independently selected from O, S, and N, and it is preferred that at least one of the heteroatoms is N. Examples of bicyclic heterocycles include (iso)indole, aza(iso)indole, (aza)indazole, (aza)benzimidazole, (aza)benztriazole, hydrothienopyridine, (iso)quinoline, hydro(iso)quinoline, hydrofuropyridine, and derivatives thereof.

[0034] The polycyclic heterocycle is preferably a 9- to 30-membered ring, and more preferably a 12- to 26-membered ring. The polycyclic heterocycle may also contain a spiro ring. When the heterocycle is a polycyclic heterocycle, it may contain up to 15 heteroatoms. Each heteroatom is independently selected from O, S, and N, and it is preferred that at least one of the heteroatoms is N. Examples of polycyclic heterocycles include carbazole, phenazine, phenoxazine, phenothiazine, benzoindole, pyrroloquinoline, acridine, and derivatives thereof.

[0035] When the heterocycle has a substituent, the substituent may be a halogen atom, a C-C 10 Examples of the substituents include hydrocarbon groups, oxygen-containing substituents such as hydroxyl groups, alkoxy groups, carbonyl groups, and carboxyl groups, nitrogen-containing substituents such as amino groups, cyano groups, and nitro groups, and sulfur-containing substituents such as sulfanyl groups, sulfoxy groups, and sulfone groups.

[0036] A １ , A ２ and A ３ When A is a heterocycle, １ , A ２ and A ３ is the same as the heterocycle defined above for X. １ A ２ or -NA １ A ２ If A １is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, A ２ may be a heterocyclic ring. １ (OA ２ ), then A １ is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, A ２ may be a heterocycle, and A １ is a heterocycle, A ２ may be a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. ３ -NA １ A ２ If A １ and A ３ is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, A ２ may be a heterocycle, and A １ is a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, A ２ and A ３ may be a heterocycle.

[0037] In X, -NA ４ A included in ４ Is = C ｎ H ２ｎ where n is an integer of 1 to 20. ｎ H ２ｎ The alkylene group represented by the formula (I) may be linear or branched. n is preferably 3 to 15, and more preferably 5 to 10.

[0038] The fluorine-containing isoxazole compound of the present embodiment has a specific substituent (-X, -CF ３, —OR or —OR′), it can have excellent effects in terms of structural expandability, and in particular, further improvement in pharmacological activity can be expected. Furthermore, since the 3-, 4-, and 5-positions on the isoxazole ring can have different substituents, it can be easily derivatized to an asymmetric structure, and its use as an intermediate is also expected. More specifically, a derivative can be obtained by modifying —OR or —OR′ by reacting a fluorine-containing isoxazole compound under acidic conditions. Furthermore, when the substituent X on the isoxazole ring is a halogen atom, a derivative can be obtained by modifying the halogen atom by reacting a fluorine-containing isoxazole compound under basic conditions. Furthermore, the fluorine-containing isoxazole compound of this embodiment is also useful in the field of electronic materials, such as organic semiconductors and liquid crystals.

[0039] (Method for Producing Fluorine-Containing Isoxazole Compound) The method for producing a fluorine-containing isoxazole compound in this embodiment includes a step of: (I) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with hydroxylamine or a salt thereof, and, optionally, a compound represented by the following general formula (5) or a salt thereof, or (II) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with an amine salt or an amine compound, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by general formula (A).

[0040] (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.

[0041] Such a fluorine-containing isoxazole compound represented by general formula (A) can be synthesized, for example, by the following method.

[0042] A first embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step of (a) reacting a fluorinated carbonyl compound represented by the following general formula (6) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (1): (In the above general formulas (1) and (6), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ５ A ６ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents, １ , A ２ and A 3each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and the wavy bond represents a single bond that represents either (E) or (Z) stereoisomerism.

[0043] A second embodiment of the method for producing a fluorinated isoxazole compound in the present embodiment includes a step (b) of reacting a fluorinated carbonyl compound represented by the following general formula (8), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (8), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎn is an integer of 1 to 20; ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0044] A third embodiment of the present invention for producing a fluorine-containing isoxazole compound includes (c) a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (9) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then further reacting the obtained reaction product with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (9), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0045] A fourth embodiment of the present invention for producing a fluorine-containing isoxazole compound includes (d) a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (10), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[0046] A fifth embodiment of the present invention for producing a fluorinated isoxazole compound includes the steps of (e) carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorinated isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0047] A sixth embodiment of the present invention for producing a fluorine-containing isoxazole compound includes the steps of (f) carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting with an alcohol, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0048] A seventh embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (g) of reacting a fluorinated carbonyl compound represented by the following general formula (13) with an amine salt or an amine compound to obtain a fluorinated isoxazole compound represented by the following general formula (2): (In the above general formulas (2) and (13), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and X represents -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２, -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ where n is an integer of 1 to 20, and the wavy bond represents a single bond that represents the (E) or (Z) stereoisomerism.

[0049] An eighth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (h) a step of reacting a fluorinated carbonyl compound represented by the following general formula (14), an amine salt or an amine compound, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorinated isoxazole compound represented by the following general formula (2): (In the above general formulas (2) and (14), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0050] A ninth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (i) a step of reacting a fluorinated carbonyl compound represented by the following general formula (15) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the obtained reaction product with an amine salt or an amine compound to obtain a fluorinated isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (15), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0051] A tenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (j) a step of reacting a fluorinated carbonyl compound represented by the following general formula (10) with an alcohol, reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resultant with an amine salt or an amine compound, thereby obtaining a fluorinated isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (10), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[0052] An eleventh embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step of (k) carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorinated isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (11), R and R′ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = Cｎ H ２ｎ and n is an integer of 1 to 20.

[0053] A twelfth embodiment of the present embodiment for producing a fluorine-containing isoxazole compound includes a step of (l) carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting the compound with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (12), R and R′ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0054] A thirteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (m) of reacting a fluorinated carbonyl compound represented by the following general formula (10) with a hydroxylamine represented by the following general formula (7) or a salt thereof, and further reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorinated isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (10), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

[0055] A fourteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (n) of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the carbonylation with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA１ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0056] A fifteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step of (o) carbonylating a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting the carbonylation with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0057] A sixteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (p) of reacting a fluoroisobutene derivative represented by the following general formula (11), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4): (In the above general formulas (4), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

[0058] A seventeenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (q) of reacting a fluoroisobutene derivative represented by the following general formula (11) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): (In the above general formulas (4-1) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[0059] An eighteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes a step (r) of reacting a fluoroisobutane derivative represented by the following general formula (12), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof, to obtain a fluorinated isoxazole compound represented by the following general formula (4): (In the above general formulas (4), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, and Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0060] A nineteenth embodiment of the present embodiment for producing a fluorinated isoxazole compound includes (s) a step of reacting a fluoroisobutane derivative represented by the following general formula (12) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): (In the above general formulas (4-1) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, Y represents a halogen atom, -OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0061] In the fluorine-containing compounds, the fluorine-containing carbonyl compound is preferably a compound represented by the above general formula (6), (8), (9), (10), (13), (14) or (15), the fluoroisobutene derivative is preferably a compound represented by the above general formula (11), and the fluoroisobutane derivative is preferably a compound represented by the above general formula (12).

[0062] In the above general formulas (5), (6), and (13), A １ , A ２ , A 3 and heterocycle are the same as defined in the fluorine-containing isoxazole compounds represented by the above-mentioned general formulae (A), (1) to (4). In the above-mentioned general formulae (4-1), (11), and (12), R' is the same as defined in the fluorine-containing isoxazole compound represented by the above-mentioned general formula (4), and the substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms in R' is preferably an alkyl group having 1 to 10 carbon atoms.

[0063] In the above general formulas (6), (8), and (9), A ５ , A ６ and A ７ is the same as the substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms defined above for R and R′, and A ５ , A ６ and A ７ The substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms in the formula (I) is preferably an alkyl group having 1 to 10 carbon atoms.

[0064] In the above general formula (12), B １ and B ２ is the same as the substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms defined above for R and R'.

[0065] In each of the above general formulas (12), Y is a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ Represents.

[0066] In Y, the halogen atom is F, Cl, Br or I, and preferably F or Cl.

[0067] In Y, -OB １ , -SO ｍ B １ B included in １ represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and is the same as the hydrocarbon group having 1 to 12 carbon atoms defined above for R and R'. Furthermore, m is an integer of 0 to 3, preferably an integer of 0 to 2, and more preferably an integer of 0 to 1.

[0068] In Y, -NB １ B ２ B included in １ and B ２ are each independently a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms. １ and B ２ may be the same or different. １ and B ２is the same as the hydrocarbon group having 1 to 12 carbon atoms defined above for R and R'.

[0069] The reaction (a) in the first embodiment is represented as the following reaction formula (A) as a whole.

[0070] The reaction (b) in the second embodiment is represented as the following reaction formula (B) as a whole.

[0071] The reaction (c) in the third embodiment is represented as the following reaction formula (C) as a whole.

[0072] The reaction (d) in the fourth embodiment is expressed as the following reaction formula (D) as a whole. In the following reaction formula, "WF" represents the cation W ＋ and F － It represents salt of.

[0073] The reaction (e) in the fifth embodiment is expressed as the following reaction formula (E) as a whole. In the following reaction formula, the nucleophile may be represented as "Nu" for convenience. Furthermore, "NuR'F" represents the reaction of the cation of the nucleophile with R' substituted with F. － It represents salt of.

[0074] The reaction (f) in the sixth embodiment is represented as the following reaction formula (F) as a whole.

[0075] The reaction (g) in the seventh embodiment is represented as the following reaction formula (G): In the following reaction formulas (G) to (O), the amine salt or amine compound may be referred to as "N compound" for convenience.

[0076] The reaction (h) in the eighth embodiment is represented as a whole by the following reaction formula (H): When the compound represented by general formula (5) or a salt thereof is not used in the reaction (h), X represents a fluorine atom (F) in the fluorine-containing isoxazole compound represented by general formula (2).

[0077] The reaction (i) in the ninth embodiment is represented as the following reaction formula (I) as a whole.

[0078] The reaction (j) in the tenth embodiment is represented as the following reaction formula (J) as a whole.

[0079] The reaction (k) in the eleventh embodiment is expressed as the following reaction formula (K) as a whole.

[0080] The reaction (l) in the twelfth embodiment is represented as the following reaction formula (L) as a whole.

[0081] The reaction (m) in the thirteenth embodiment is represented as the following reaction formula (M) as a whole.

[0082] The reaction (n) in the fourteenth embodiment is expressed as the following reaction formula (N) as a whole.

[0083] The reaction (o) in the fifteenth embodiment is represented as the following reaction formula (O) as a whole.

[0084] The reaction (p) in the sixteenth embodiment is represented as the following reaction formula (P) as a whole.

[0085] The reaction (q) in the seventeenth embodiment is represented as the following reaction formula (Q) as a whole.

[0086] The reaction (r) in the eighteenth embodiment is represented as the following reaction formula (R) as a whole.

[0087] The reaction (s) in the nineteenth embodiment is represented as the following reaction formula (S) as a whole.

[0088] In each of the above reactions, the hydroxylamine represented by the general formula (7) and the compound represented by the general formula (5) may each be in the form of a salt. When the hydroxylamine represented by the general formula (7) is in the form of a salt, the moiety constituting the amino group of the hydroxylamine (—NH ２ ) moiety is cationized (-NH ３ ＋ ) and forms a salt with a counter ion. When the compound represented by general formula (5) is in the form of a salt, the H moiety of the compound is cationized to form (H ＋ The counter ion is not particularly limited as long as it is a monovalent anion, and examples thereof include F － , Cl － ,Br － , I － and the like, trifluoroacetate anion, paratoluenesulfonate anion, trifluoromethanesulfonate anion, nonafluorobutanesulfonic acid, bis(trifluoromethylsulfonyl)imide anion, tetrafluoroborate anion, and the like.

[0089] In each of the above reactions, when an amine salt or an amine compound is used, the amine salt or the amine compound has one amino group (—NH ２ a nitrogen-containing heterocyclic cation in which one amino group (-NH) is bonded to a nitrogen atom in the heterocyclic ring; ２ amine salts of a quaternary ammonium cation having a substituted ammonium group (III) bonded to the nitrogen atom with an anion selected from halogens, sulfates, phosphates, sulfonic acids, trifluoroacetic acids, tetrafluoroborate, tetraphenylborate, hexafluoroborate, and sulfonylimide acids; primary amines, hydroxylamines, or amine salts having an anionic substituent or anion selected from halogens, sulfates, phosphates, sulfonic acids, and trifluoroacetic acids; or quaternary ammonium salts substituted with a hydrocarbon group selected from alkyl groups and aryl groups.

[0090] In the nitrogen-containing heterocyclic cation, at least one nitrogen atom is contained as a heteroatom in the heterocycle, and may be optionally substituted. In addition, when the nitrogen atom on the nitrogen-containing heterocycle is substituted with one amino group (—NH ２ ) is directly bonded to the nitrogen-containing heterocyclic cation, and the nitrogen-containing heterocyclic cation is preferably a monocyclic heterocycle. The nitrogen-containing heterocycle may further contain at least one heteroatom selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom (O) as a ring-constituting atom. The nitrogen-containing heterocycle is preferably an aromatic heterocycle, and the number of ring members is preferably 5 to 8, and more preferably 5 or 6. Examples of such nitrogen-containing heterocycles include pyridine, 4-dimethylaminopyridine, and 1-methylimidazole.

[0091] One amino group (-NH ２ In a quaternary ammonium cation in which a substituted ammonium group (C1) is bonded to the nitrogen atom, the nitrogen atom of the quaternary ammonium cation is preferably bonded to a hydrocarbon group selected from an alkyl group and an aryl group as another substituent. The alkyl group preferably has 1 to 12 carbon atoms and may be linear or branched. Examples of such alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl groups. The aryl group preferably has 6 to 12 carbon atoms and may be substituted with a methyl group or the like. Examples of such aryl groups include tolyl and mesityl groups.

[0092] In the primary amine, hydroxylamine, or amine salt having the above-mentioned anionic substituent or anion, it is preferred that the anionic substituent or anion is directly bonded to a nitrogen atom constituting the amine. In addition, in the hydroxylamine having the above-mentioned anionic substituent or anion, it is preferred that the oxygen atom (—O—NH ２ It is preferred that the anionic substituent or anion is directly bonded to the alkyl group.

[0093] In the quaternary ammonium salt, the nitrogen atom of the quaternary ammonium salt is substituted with a hydrocarbon group selected from an alkyl group and an aryl group, and the nitrogen atom of the quaternary ammonium salt is substituted with an amino group (—NH ２ ) is not bonded to the alkyl group. The alkyl group preferably has 1 to 12 carbon atoms and may be linear or branched. Examples of such alkyl groups include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group, and a dodecyl group. The aryl group preferably has 6 to 12 carbon atoms and may be substituted with methyl or the like. Examples of such aryl groups include a tolyl group and a mesityl group.

[0094] Specific examples of the amine salt and amine compound include 1-aminopyridinium iodide, tetrabutylammonium azide, hydroxylamine-O-sulfonic acid, 1-aminopyridinium mesitylenesulfonate, O-(mesitylenesulfonyl)hydroxylamine, 1,1,1-trimethylhydrazinium trifluoroacetate, and the like.

[0095] In each of the above reactions, when a nucleophile is used, examples of the nucleophile include tertiary amines such as triethylamine, quinuclidine, and 1,4-diazabicyclo[2.2.2]octane, imidazole derivatives such as 1-methylimidazole, and pyridine derivatives such as pyridine and 4-dimethylaminopyridine.

[0096] When a base is used in each of the above reactions, examples of the base include inorganic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium fluoride, and potassium fluoride; organic nitrogen derivatives such as pyridine, triethylamine, diisopropylethylamine, diazabicyclononene, diazabicycloundecene, methyltriazabicyclodecene, and diazabicyclooctane; and phosphorus derivatives such as phosphazene bases.

[0097] In each of the above reactions, when an alcohol (ROH) is used, the type of alcohol is not particularly limited as long as it can form an ester of the alcohol with 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid, and an appropriate alcohol can be used depending on the desired structure of isoxazole.

[0098] When hydrogen fluoride (HF) is generated in the method for producing a fluorinated isoxazole compound according to the present embodiment, for example, a hydrogen halide scavenger may be used. By using the hydrogen halide scavenger, the step of recovering hydrogen fluoride can be omitted, and the fluorinated isoxazole compound represented by the general formula (A) can be obtained more simply.

[0099] In the reaction (a) above, a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (6) and the amino group of the hydroxylamine represented by general formula (7). The 3- and 4-positions of the formed isoxazole structure are provided with X and CF of the fluorine-containing carbonyl compound represented by general formula (6). ３ are located at the 5-position of the isoxazole structure, and an OH group formed as a result of the formation of the ring structure is located at the 5-position of the isoxazole structure.

[0100] In the reaction (b) above, a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (8) and the amino group of the hydroxylamine represented by general formula (7), the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. CF of the fluorine-containing carbonyl compound represented by general formula (8) is located at the 4-position of the formed isoxazole structure. ３ is located.

[0101] In the above reaction (c), a cyclic isoxazole structure is formed between the reaction product obtained by reacting a fluorine-containing carbonyl compound represented by general formula (9) with a compound represented by general formula (5) in the presence of a base and the amino group of the hydroxylamine represented by general formula (7), the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. CF of the fluorine-containing carbonyl compound represented by general formula (9) is located at the 4-position of the formed isoxazole structure. ３ is located.

[0102] In the above reaction (d), a cyclic isoxazole structure is formed between the reaction product obtained by reacting an intermediate reactant obtained by reacting a fluorine-containing carbonyl compound represented by general formula (10) with an alcohol and a compound represented by general formula (5) in the presence of a base, and the amino group of hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. CF of the fluorine-containing carbonyl compound represented by general formula (10) is located at the 4-position of the formed isoxazole structure. ３ is located.

[0103] In the above reaction (e), a fluoroisobutene derivative represented by general formula (11) is carbonylated in the presence of a nucleophile, and the intermediate reactant obtained by further reacting with an alcohol is reacted with a compound represented by general formula (5) in the presence of a base to form a reaction product, and a cyclic isoxazole structure is formed between the amino group of hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. At the 4-position of the formed isoxazole structure, CF of the fluoroisobutene derivative represented by general formula (11) is ３ is located.

[0104] In the above reaction (f), a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by general formula (12) is carbonylated in the presence of a nucleophile, and the intermediate reactant obtained by further reacting with an alcohol is reacted with a compound represented by general formula (5) in the presence of a base to form a reaction product and the amino group of hydroxylamine represented by general formula (7), and a cyclic isoxazole structure is formed between the reaction product and the amino group of hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and the OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. At the 4-position of the formed isoxazole structure, CF of the fluorine-containing carbonyl compound represented by general formula (12) is ３ is located.

[0105] In the reaction (g) above, a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (13) and the amino group of the amine salt or amine compound. The 3-, 4-, and 5-positions of the formed isoxazole structure are each independently selected from X, CF, and CF of the fluorine-containing carbonyl compound represented by general formula (13). ３ and OR are located respectively.

[0106] In the reaction (h) above, a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (14) and the amino group of the amine salt or amine compound. The CF of the fluorine-containing carbonyl compound represented by general formula (14) is attached to the 4- and 5-positions of the formed isoxazole structure. ３ When the fluorine-containing carbonyl compound represented by general formula (14) is further reacted with the compound represented by general formula (5), the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and when the compound represented by general formula (5) is not used, F contained in the fluorine-containing carbonyl compound represented by general formula (14) is located at the 3-position of the isoxazole structure.

[0107] In the above reaction (i), a cyclic isoxazole structure is formed between the reaction product obtained by reacting a fluorine-containing carbonyl compound represented by general formula (15) with a compound represented by general formula (5) in the presence of a base and the amino group of the amine salt or amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. At the 4- and 5-positions of the formed isoxazole structure, CF possessed by the fluorine-containing carbonyl compound represented by general formula (15) is substituted. ３ and OR are located respectively.

[0108] In the above reaction (j), a cyclic isoxazole structure is formed between the reaction product obtained by reacting an intermediate reactant, obtained by reacting a fluorine-containing carbonyl compound represented by general formula (10) with an alcohol, with a compound represented by general formula (5) in the presence of a base, and the amino group of the amine salt or amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. The CF of the fluorine-containing carbonyl compound represented by general formula (10) is substituted at the 4-position of the formed isoxazole structure. ３ At the 5-position of the isoxazole structure, OR is located, which is contained in the intermediate reactant obtained by reacting the fluorine-containing carbonyl compound represented by general formula (10) with an alcohol (ROH).

[0109] In the above reaction (k), a fluoroisobutene derivative represented by general formula (11) is carbonylated in the presence of a nucleophile, and the intermediate reactant obtained by further reacting with an alcohol is reacted with a compound represented by general formula (5) in the presence of a base to form a reaction product, which is then reacted with the amino group of the amine salt or amine compound to form a cyclic isoxazole structure, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. The CF of the fluorine-containing carbonyl compound represented by general formula (11) is substituted at the 4-position of the formed isoxazole structure. ３ At the 5-position of the isoxazole structure, there is located OR, which is contained in an intermediate reactant obtained by reacting a compound obtained by carbonylating a fluoroisobutene derivative represented by general formula (11) with an alcohol (ROH).

[0110] In the above reaction (l), a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by general formula (12) is carbonylated in the presence of a nucleophile, and the intermediate reactant obtained by further reacting with an alcohol is reacted with a compound represented by general formula (5) in the presence of a base to form a reaction product, which is then reacted with the amino group of an amine salt or an amine compound to form a cyclic isoxazole structure between the reaction product and the amino group of an amine compound, and the compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure. ３ At the 5-position of the isoxazole structure, there is located OR, which belongs to an intermediate reactant obtained by reacting an alcohol (ROH) with a compound obtained by performing an elimination reaction of a fluoroisobutene derivative represented by general formula (12), followed by carbonylation.

[0111] In the reaction (m) above, a cyclic isoxazole structure is formed between the fluorine-containing carbonyl compound represented by general formula (10) and the amino group of the hydroxylamine represented by general formula (7). The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. CF of the fluorine-containing carbonyl compound represented by general formula (10) is located at the 4-position of the formed isoxazole structure. ３ is located.

[0112] In the above reaction (n), a fluoroisobutene derivative represented by general formula (11) is carbonylated in the presence of a nucleophile, and the intermediate reactant obtained by further reacting with an alcohol is reacted with a compound represented by general formula (5) in the presence of a base to obtain a reaction product, which forms a cyclic isoxazole structure between the amino group of hydroxylamine represented by general formula (7). The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. CF possessed by the fluoroisobutene derivative represented by general formula (11) is located at the 4-position of the formed isoxazole structure. ３ is located.

[0113] In the above reaction (o), a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by general formula (12) is carbonylated in the presence of a nucleophile, and the intermediate reactant obtained by further reacting with an alcohol is reacted with a compound represented by general formula (5) in the presence of a base to obtain a reaction product, which forms a cyclic isoxazole structure between the amino group of hydroxylamine represented by general formula (7). The compound represented by general formula (5) is substituted at the 3-position of the isoxazole structure, and OH formed due to the formation of the ring structure is located at the 5-position of the isoxazole structure. The CF of the fluoroisobutene derivative represented by general formula (12) is located at the 4-position of the formed isoxazole structure. ３ is located.

[0114] In the reaction (p) above, a cyclic isoxazole structure is formed between the fluoroisobutylene derivative represented by general formula (11) and the amino group of the hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is substituted on the isoxazole structure. The -OR' and CF of the fluoroisobutylene derivative are respectively substituted at the 3- and 4-positions of the formed isoxazole structure. ３ is located at the 5-position of the isoxazole structure, and X in the compound represented by general formula (5) is located at the 5-position of the isoxazole structure.

[0115] In the reaction (q) above, a cyclic isoxazole structure is formed between the fluoroisobutylene derivative represented by general formula (11) and the amino group of the hydroxylamine represented by general formula (7). The 3-, 4-, and 5-positions of the formed isoxazole structure are each provided with -OR', CF which the fluoroisobutylene derivative has. ３ and F are located.

[0116] In the reaction (r) above, a cyclic isoxazole structure is formed between the fluoroisobutane derivative represented by general formula (12) and the amino group of the hydroxylamine represented by general formula (7), and the compound represented by general formula (5) is substituted on the isoxazole structure. The -OR' and CF of the fluoroisobutane derivative are respectively substituted at the 3- and 4-positions of the formed isoxazole structure.３ are located at the 5-position of the isoxazole structure, and X in the compound represented by general formula (5) is located at the 5-position of the isoxazole structure.

[0117] In the reaction (s) above, a cyclic isoxazole structure is formed between the fluoroisobutane derivative represented by general formula (12) and the amino group of the hydroxylamine represented by general formula (7). The 3-, 4-, and 5-positions of the formed isoxazole structure are each provided with -OR', CF, which the fluoroisobutane derivative has. ３ and F are located.

[0118] The hydrogen halide scavenger is a substance that has the function of capturing the hydrogen fluoride (HF) that is produced. Examples of the hydrogen halide scavenger include inorganic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium fluoride, and potassium fluoride, organic nitrogen derivatives such as pyridine, triethylamine, diisopropylethylamine, diazabicyclononene, diazabicycloundecene, methyltriazabicyclodecene, and diazabicyclooctane, and phosphorus derivatives such as phosphazene bases.

[0119] Each of the above reactions (a) to (s) may be carried out in the presence of a fluoride ion scavenger, if necessary. The fluoride ion scavenger is preferably a salt of a cation of lithium, sodium, magnesium, potassium, calcium, or tetramethylammonium with an anion of trifluoroacetic acid, heptafluorobutyric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, trifluoromethanesulfonic acid, nonafluorobutanesulfonic acid, bis(trifluoromethanesulfonyl)imide, bis(nonafluorobutanesulfonyl)imide, N,N-hexafluoropropane-1,3-disulfonylimide, tetraphenylboric acid, tetrakis[3,5-bis(trifluoromethyl)phenyl]boric acid, or tetrakis(pentafluorophenyl)boric acid. Among these, potassium salts or sodium salts are preferred, and sodium salts are more preferred. It is believed that the cations derived from the fluoride ion scavenger capture fluorine ions liberated during the reaction and precipitate as a salt that has low solubility in organic solvents, thereby accelerating the reaction and enabling the production of a fluorinated isoxazole compound in high yield.

[0120] The reaction temperature in the above reactions (a) to (s) is preferably 0 to 100° C., more preferably 5 to 50° C., and even more preferably 10 to 20° C. The reaction time in the above reactions (a) to (s) is preferably 0.5 to 48 hours, more preferably 1 to 36 hours, and even more preferably 2 to 12 hours.

[0121] The solvent used in the above reactions (a) to (s) is preferably an organic solvent, and examples thereof include aprotic polar solvents such as tetrahydrofuran, monoglyme, diglyme, triglyme, tetraglyme, acetonitrile, dimethylformamide, dimethylacetamide, methylpyrrolidone, 4-methyltetrahydropyran, dimethylethyleneurea, tetramethylurea, dimethyl sulfoxide, and sulfolane, and two-phase solvents consisting of a protic polar solvent such as methanol or water and a non-aqueous solvent such as dichloromethane, toluene, and diethyl ether. Furthermore, as a catalyst for the above reactions (a) to (s), a quaternary ammonium halide such as benzyltriethylammonium chloride, a quaternary phosphonium halide, a crown ether, or the like can be optionally used.

[0122] Based on the above embodiments, the present invention relates to the following [1] to

[25] : [1] A fluorine-containing isoxazole compound represented by the following general formula (A): (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; Y １ and Y ２each independently represents N or O and is different from each other.) [2] The fluorine-containing isoxazole compound according to the above [1], which is a compound represented by the following general formula (1): (In the above general formula (1), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20. [3] The fluorinated isoxazole compound according to the above [1], which is a compound represented by the following general formula (2): (In the above general formula (2), R represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎand n is an integer of 1 to 20. [4] The fluorinated isoxazole compound according to the above [1], which is a compound represented by the following general formula (3): (In the above general formula (3), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20. [5] The fluorine-containing isoxazole compound according to the above [1], which is a compound represented by the following general formula (4): (In the above general formula (4), R' represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎand n is an integer of 1 to 20.) [6] A method for producing a fluorine-containing isoxazole compound, comprising the steps of: (I) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with hydroxylamine or a salt thereof, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by the following general formula (A): (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.) [7] A method for producing a fluorine-containing isoxazole compound according to the above item [6], which comprises a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (6) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (6) and (7), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ５ A ６ , -NA ５ A ６ , -NA ５ (OA ６ ), or -NA ７ -NA ５ A ６ represents, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and the wavy bond represents a single bond showing stereoisomerism of (E) or (Z).) [8] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (8), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof, to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (8), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ and each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.) [9] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (9) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then further reacting the resulting reaction product with a hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (9), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ and each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[10] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (10), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation or a phosphonium cation.)

[11] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.)

[12] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[13] A method for producing a fluorinated isoxazole compound according to the above item [6], comprising a step of reacting a fluorinated carbonyl compound represented by the following general formula (13) with an amine salt or an amine compound to obtain a fluorinated isoxazole compound represented by the following general formula (2): (In the above general formulas (2) and (13), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and X represents -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle,１ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ wherein n is an integer of 1 to 20, and the wavy bond represents a single bond representing the stereoisomerism of (E) or (Z).

[14] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (14), an amine salt or an amine compound, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (14), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.)

[15] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (15) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (15), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, or a heterocycle; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.)

[16] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (10), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation or a phosphonium cation.)

[17] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of: carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting reaction product with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (11), R and R′ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎand n is an integer of 1 to 20.)

[18] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with an amine salt or an amine compound, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (12), R and R′ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[19] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with a hydroxylamine represented by the following general formula (7) or a salt thereof, and further reacting the obtained reaction product with a compound represented by the following general formula (5) or a salt thereof, thereby obtaining a fluorine-containing isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (10), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation or a phosphonium cation.)

[20] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the resulting compound with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.)

[21] A method for producing a fluorine-containing isoxazole compound according to the above item [6], comprising the steps of carbonylating a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting the resulting compound with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[22] A method for producing a fluorinated isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof, to obtain a fluorinated isoxazole compound represented by the following general formula (4): (In the above general formulas (4), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎand n is an integer of 1 to 20.)

[23] A method for producing a fluorinated isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): (In the above general formulas (4-1) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[24] A method for producing a fluorinated isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof, to obtain a fluorinated isoxazole compound represented by the following general formula (4): (In the above general formulas (4), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.)

[25] A method for producing a fluorinated isoxazole compound according to the above item [6], comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12) with a hydroxylamine represented by the following general formula (7) to obtain a fluorinated isoxazole compound represented by the following general formula (4-1): (In the above general formulas (4-1) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, Y represents a halogen atom, -OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

[0123] Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, but includes all aspects encompassed by the concept of the present invention and the scope of the claims, and can be modified in various ways within the scope of the present invention.

[0124] Examples of the present invention will be described below, but the present invention is not limited to these examples as long as they do not deviate from the spirit of the present invention. Note that the room temperature described below is in the range of 20°C ± 10°C.

[0125] Example 1: Preparation of 3-methoxy-4-(trifluoromethyl)-5-hydroxyisoxazole. Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride was dissolved in 75 g of methanol. Subsequently, 5.7 g (56 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C. Next, 2.7 g (14 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)acrylate was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, a 1N aqueous solution of hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.2 g of the compound represented by the following formula (16). The isolation yield of the obtained compound was 8%.

[0126]

[0127] The analytical results were as follows: Mass spectrum (APCI, m / z): 183 ([M] ＋ )

[0128] Example 2: Preparation of 3-ethoxy-4-(trifluoromethyl)-5-hydroxyisoxazole. Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride was dissolved in 75 g of ethanol. Subsequently, 5.7 g (56 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C. Next, 2.7 g (14 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)acrylate was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, a 1N aqueous solution of hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.4 g of the compound represented by the following formula (17). The isolation yield of the obtained compound was 13%.

[0129]

[0130] The analytical results were as follows: Mass spectrum (APCI, m / z): 197 ([M] ＋ )

[0131] Example 3 Preparation of 3-(dibenzylamino)-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 3.9 g (47 mmol) of 1-methylimidazole was added to 20 g of tetrahydrofuran. Subsequently, 10 g (47 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1,3-dimethylimidazolium cation was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 5.6 g (47 mmol) of 2-(2-methoxyethoxy)ethanol and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 9.3 g (47 mmol) of dibenzylamine, 9.5 g (94 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl (E / Z)-3-(dibenzylamino)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixed solution of 1.6 g (47 mmol) of hydroxylamine, 9.5 g (94 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, a 1N aqueous hydrochloric acid solution was added to the reaction mixture to adjust the pH to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (18). The isolated yield of the compound was 3%.

[0132]

[0133] The analytical results were as follows: Mass spectrum (APCI, m / z): 348 ([M] ＋ )

[0134] Example 4 Preparation of 3-(dibenzylamino)-4-(trifluoromethyl)-5-hydroxyisoxazole using methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate instead of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene in Example 3. 1.9 g (9.5 mmol) of dibenzylamine and 1.9 g (19 mmol) of triethylamine were added to 30 g of tetrahydrofuran under ice-water cooling. Subsequently, 2.0 g (9.5 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was added dropwise so that the internal temperature did not exceed 10°C. After approximately 16 hours, a reaction mixture containing methyl (E / Z)-3-(dibenzylamino)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixed solution of 0.3 g (9.5 mmol) of hydroxylamine, 1.9 g (19 mmol) of triethylamine, and 30 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, a 1N aqueous solution of hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate = 7:3), and purified using a silica gel column. Analytical results were similar to those of the product in Example 3.

[0135] Example 5 Preparation of 3-(1-azonanyl)-4-(trifluoromethyl)-5-hydroxyisoxazole 3.6 g (30 mmol) of 2-(2-methoxyethoxy)ethanol was added to 30 g of tetrahydrofuran under ice-water cooling. Subsequently, 10 g (30 mmol) of a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1-methyl-4-dimethylaminopyridinium cation was added dropwise to a mixed solution of 30 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 8 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 3.8 g (30 mmol) of azonane, 6.1 g (60 mmol) of triethylamine, and 30 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl (E / Z)-3-(1-azonanyl)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixed solution of 1.0 g (30 mmol) of hydroxylamine, 6.1 g (60 mmol) of triethylamine, and 30 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, a 1N aqueous hydrochloric acid solution was added to the reaction mixture so that the pH was approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.9 g of the compound represented by the following formula (19). The isolated yield of the compound was 11%.

[0136]

[0137] The analytical results were as follows: Mass spectrum (APCI, m / z): 278 ([M] ＋ )

[0138] Example 6 Preparation of 3-(1-azonanyl)-4-(trifluoromethyl)-5-hydroxyisoxazole using methyl (E / Z)-3-(1-azonanyl)-3-fluoro-2-(trifluoromethyl)acrylate instead of the salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1-methyl-4-dimethylaminopyridinium cation in Example 5. 1.9 g (27 mmol) of hydroxylamine hydrochloride was dissolved in 60 g of methanol under ice-water cooling. Subsequently, 8.2 g (81 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C. Next, 5 g (27 mmol) of methyl (E / Z)-3-(1-azonanyl)-3-fluoro-2-(trifluoromethyl)acrylate was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 16 hours, a 1N aqueous solution of hydrochloric acid was added to the reaction mixture to adjust the pH to about 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column. The analytical results were the same as those of the product in Example 5.

[0139] Example 7 Preparation of 3-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)-4-(trifluoromethyl)-5-hydroxyisoxazole Under ice-water cooling, 20 g (86 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane was added to 80 g of tetrahydrofuran. Subsequently, 11 g (86 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 8.7 g (86 mmol) of triethylamine and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and triethylmethylammonium cation was obtained. This reaction mixture was added dropwise to a mixed solution of 10 g (86 mmol) of 2-(2-methoxyethoxy)ethanol and 20 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 8 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 12 g (86 mmol) of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine, 22 g (172 mmol) of diisopropylethylamine, and 40 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After about 16 hours, a reaction mixture containing 2-(2-methoxyethoxy)ethyl (E / Z)-3-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)-3-fluoro-2-(trifluoromethyl)acrylate was obtained. This reaction mixture was added dropwise to a mixed solution of 2.8 g (86 mmol) of hydroxylamine, 22 g (172 mmol) of diisopropylethylamine, and 30 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After about 16 hours, a 1N aqueous hydrochloric acid solution was added to adjust the pH of the reaction mixture to about 5, and ammonium chloride was added until saturated.The organic phase was dried over sodium sulfate, dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (20). The isolated yield of the compound was 2%.

[0140]

[0141] The analytical results were as follows: Mass spectrum (APCI, m / z): 290 ([M] ＋ )

[0142] Example 8 Preparation of 3-amino-N,N-dibenzyl-5-methoxy-4-(trifluoromethyl)isoxazole Under ice-water cooling, 1.1 g (3.0 mmol) of methyl 3-(dibenzylamino)-3-fluoro-2-(trifluoromethyl)-2-propenoate was added to 30 g of tetrahydrofuran, and 0.7 g (3.0 mmol) of 1-aminopyridinium iodide was further dissolved therein. Subsequently, 0.8 g (6.0 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified with a silica gel column to obtain 0.2 g of the compound represented by the following formula (21). The isolated yield of the obtained compound was 15%.

[0143]

[0144] The analytical results were as follows: Mass spectrum (APCI, m / z): 362 ([M] ＋ ) １ H-NMR (400MHz, CDCl ３ ) δppm: 7.33-7.24 (m, 10H), 4.65 (s, 4H), 3.86 (s, 3H)

[0145] Example 9 Preparation of 3-fluoro-5-methoxy-4-(trifluoromethyl)isoxazole Under ice-water cooling, 0.6 g (3.0 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)acrylate was added to 20 g of tetrahydrofuran. Subsequently, a solution of 0.9 g (3.0 mmol) of tetrabutylammonium azide in 20 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 72 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified with a silica gel column to obtain 0.1 g of the compound represented by the following formula (22). The isolated yield of the obtained compound was 25%.

[0146]

[0147] The analytical results were as follows: Mass spectrum (APCI, m / z): 185 ([M] ＋ )

[0148] Example 10 Preparation of 4-(3-(5-methoxy-4-(trifluoromethyl))isoxazolyl)thiomorpholine 1,1-dioxide Under ice-water cooling, 0.3 g (2.0 mmol) of thiomorpholine 1,1-dioxide and 0.5 g (4.0 mmol) of diisopropylethylamine were added to 20 g of tetrahydrofuran. Subsequently, 0.4 g (2.0 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, the contents were cooled with ice-water, and 0.2 g (2.0 mmol) of hydroxylamine-O-sulfonic acid was added so that the internal temperature did not exceed 10°C. Subsequently, 0.8 g (6.0 mmol) of diisopropylethylamine was added dropwise, and the temperature was raised to room temperature. After about 36 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.1 g of the compound represented by the following formula (23). The isolated yield of the obtained compound was 9%.

[0149]

[0150] The analytical results were as follows: Mass spectrum (APCI, m / z): 300 ([M] ＋ )

[0151] Example 11 Preparation of 5-ethoxy-3-((4-methoxybenzyl)oxy)-4-(trifluoromethyl)isoxazole Under ice-water cooling, 0.5 g (10.0 mmol) of ethanol was added to 20 g of tetrahydrofuran. Subsequently, a mixed solution of 3.0 g (9.0 mmol) of a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1-methyl-4-dimethylaminopyridinium cation dissolved in 30 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, the reaction mixture was cooled with ice-water, and a mixed solution of 1.2 g (9.0 mmol) of 4-methoxybenzyl alcohol, 1.8 g (18.0 mmol) of triethylamine, and 30 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, the reaction mixture was cooled with ice water, and 2.6 g (9.0 mmol) of 1-aminopyridinium mesitylenesulfonate was added so that the internal temperature did not exceed 10°C. Subsequently, 2.3 g (18.0 mmol) of diisopropylethylamine was added dropwise, and the temperature was raised to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.2 g of the compound represented by the following formula (24). The isolated yield of the obtained compound was 8%.

[0152]

[0153] The analytical results were as follows: Mass spectrum (APCI, m / z): 317 ([M] ＋ )

[0154] Example 12 Preparation of 3-amino-5-((2-ethylhexyl)oxy)-N-methyl-N-(3-pyridyl)-4-(trifluoromethyl)isoxazole Under ice-water cooling, 3.9 g (47.0 mmol) of 1-methylimidazole was added to 20 g of tetrahydrofuran. Subsequently, 10 g (47.0 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and 1,3-dimethylimidazolium cation was obtained. This reaction mixture was added dropwise to a mixed solution of 6.1 g (47.0 mmol) of 2-ethyl-1-hexanol and 20 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was then warmed to room temperature. After approximately 8 hours, a reaction mixture containing 2-ethylhexyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 5.1 g (47.0 mmol) of 3-(methylamino)pyridine, 9.5 g (94.0 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was then warmed to room temperature. After approximately 16 hours, this reaction mixture was added dropwise to a mixed solution of 10 g (47.0 mmol) of o-(mesitylenesulfonyl)hydroxylamine, 9.5 g (94.0 mmol) of triethylamine, and 20 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was allowed to warm to room temperature. After approximately 16 hours, a 1N aqueous solution of hydrochloric acid was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (25). The isolated yield of the obtained compound was 3%.

[0155]

[0156] The analytical results were as follows: Mass spectrum (APCI, m / z): 371 ([M] ＋ )

[0157] Example 13 Preparation of 4-(3-(5-(2-methoxy)ethoxy-4-(trifluoromethyl))isoxazolyl)-2-piperazinone Under ice-water cooling, 20 g (86.0 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane was added to 80 g of tetrahydrofuran. Subsequently, 11 g (86.0 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After about 8 hours, a reaction mixture containing 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was obtained. Under ice-water cooling, this reaction mixture was added dropwise to a mixed solution of 9.6 g (86.0 mmol) of quinuclidine and 20 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, a reaction mixture containing a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and N-methylquinuclidinium cation was obtained. This reaction mixture was added dropwise to a mixed solution of 6.5 g (86.0 mmol) of 2-methoxyethanol and 20 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 8 hours, a reaction mixture containing 2-methoxyethyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate was obtained. This reaction mixture was added dropwise to a mixed solution of 8.6 g (86.0 mmol) of piperazinone, 22 g (172.0 mmol) of diisopropylethylamine, and 40 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, this reaction mixture was added dropwise to a mixed solution of 16 g (86.0 mmol) of 1,1,1-trimethylhydrazinium trifluoroacetate, 22 g (172.0 mmol) of diisopropylethylamine, and 30 g of tetrahydrofuran under ice-water cooling, so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After approximately 16 hours, a 1N aqueous hydrochloric acid solution was added to adjust the pH of the reaction mixture to approximately 5, and ammonium chloride was added until saturated. The organic phase was dried over sodium sulfate, then dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3), and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (26). The isolation yield of the obtained compound was 2%.

[0158]

[0159] The analytical results were as follows: Mass spectrum (APCI, m / z): 309 ([M] ＋ )

[0160] Example 14 Preparation of 5-(1H-benzo[d][1,2,3]triazol-1-yl)-4-(trifluoromethyl)isoxazol-3-ol Under ice-water cooling, 2 g (6.4 mmol) of hydroxylammonium bistrifluoromethanesulfonylimide was dissolved in 30 g of tetrahydrofuran. Subsequently, a mixed solution of 1.9 g (6.4 mmol) of a salt of 3,3,3-trifluoro-2-(trifluoromethyl)propanoic acid fluoride anion and N-methylimidazolium cation dissolved in 20 g of tetrahydrofuran was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 3 hours, the reaction mixture was cooled with ice-water, and 0.7 g (6.4 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 4 hours, the reaction mixture was cooled with ice water and added dropwise to a mixed solution of 0.8 g (6.4 mmol) of 1,2,3-benzotriazole, 2.3 g (23.0 mmol) of triethylamine, and 30 g of tetrahydrofuran, so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified with a silica gel column to obtain 0.3 g of the compound represented by the following formula (27). The isolated yield of the obtained compound was 17%.

[0161]

[0162] The analytical results were as follows: Mass spectrum (APCI, m / z): 270 ([M] ＋ ) １ H-NMR (400MHz, CDCl ３ ) δppm: 8.19 (dd, 1H), 8.12 (dd, 1H), 7.41 (ddd, 1H), 7.33 (ddd, 1H)

[0163] Example 15 Preparation of 5-(10H-spiro[acridine-9,9'-fluoren]-10-yl)-4-(trifluoromethyl)isoxazol-3-ol Under ice-water cooling, 0.9 g (8.5 mmol) of triethylamine was added to 20 g of acetonitrile. Subsequently, 1.8 g (8.5 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 4 hours, under ice-water cooling, the reaction mixture was added dropwise to a mixed solution of 3.0 g (8.5 mmol) of hydroxylammonium tetraphenylborate and 20 g of acetonitrile so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 3 hours, the reaction mixture was cooled with ice-water, and 0.9 g (8.5 mmol) of triethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 4 hours, the reaction mixture was added dropwise to a mixed solution of 2.8 g (8.5 mmol) of 10H-spiro[acridine-9,9'-fluorene], 3.0 g (30.0 mmol) of triethylamine, and 20 g of acetonitrile under ice-water cooling, so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified with a silica gel column to obtain 0.4 g of the compound represented by the following formula (27). The isolated yield of the obtained compound was 10%.

[0164]

[0165] The analytical results were as follows: Mass spectrum (APCI, m / z): 482 ([M] ＋ )

[0166] Example 16 Production of 5-((2,2,4,4-tetramethylpentan-3-ylidene)amino)-4-(trifluoromethyl)isoxazol-3-ol Under ice-water cooling, 1.1 g (4.8 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane was added to 40 g of tetrahydrofuran. Subsequently, 0.6 g (4.8 mmol) of diisopropylethylamine was added dropwise thereto so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After about 4 hours, under ice-water cooling, the reaction mixture was added dropwise to a mixed solution of 0.6 g (4.8 mmol) of 4-dimethylaminopyridine and 15 g of tetrahydrofuran so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After about 4 hours, the reaction mixture was added dropwise to a mixed solution of 1.5 g (4.8 mmol) of hydroxylammonium bistrifluoromethanesulfonylimide and 20 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After about 3 hours, the reaction mixture was cooled with ice-water, and 0.6 g (4.8 mmol) of diisopropylethylamine was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After about 4 hours, the reaction mixture was added dropwise to a mixed solution of 0.7 g (4.8 mmol) of 2,2,4,4-tetramethyl-3-pentanoneimine, 2.8 g (22.0 mmol) of diisopropylethylamine, and 20 g of tetrahydrofuran under ice-water cooling so that the internal temperature did not exceed 10°C, and the mixture was warmed to room temperature. After about 16 hours, the contents were dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column, yielding 0.1 g of the compound represented by the following formula (28). The isolated yield of the obtained compound was 9%.

[0167]

[0168] The analytical results were as follows: Mass spectrum (APCI, m / z): 292 ([M] ＋ )

[0169] Example 17 Preparation of 5-fluoro-3-methoxy-4-trifluoromethylisoxazole Under ice-water cooling, 3.1 g (10.0 mmol) of hydroxylammonium bis(trifluoromethylsulfonyl)amine and 2.1 g (10.0 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 75 g of 4-methyltetrahydropyran. Subsequently, a solution of 4.7 g (20.0 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 25 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After about 16 hours, the mixture was cooled with ice water, and a solution of 6.1 g (26.0 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 20 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified with a silica gel column to obtain 0.04 g of the compound represented by the following formula (29). The isolated yield of the obtained compound was 2%.

[0170]

[0171] The analytical results were as follows: Mass spectrum (APCI, m / z): 185 ([M] ＋ )

[0172] Example 18 Preparation of 3-methoxy-5-morpholinyl-4-trifluoromethylisoxazole Under ice-water cooling, 0.7 g (10.0 mmol) of hydroxylamine hydrochloride and 2.1 g (10.0 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 30 g of methanol. Subsequently, a solution of 2.0 g (20.0 mmol) of triethylamine in 10 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 4.5 g (52.0 mmol) of morpholine in 15 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After approximately 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.5 g of the compound represented by the following formula (30). The isolated yield of the obtained compound was 18%.

[0173]

[0174] The analytical results were as follows: Mass spectrum (APCI, m / z): 252 ([M] ＋ ) １ H-NMR (400MHz, CDCl ３ ) δppm: 3.80 (m, 7H), 3.50 (dd, 4H)

[0175] Example 19: Preparation of 5-fluoro-3-methoxy-4-trifluoromethylisoxazole using 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane instead of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene in Example 17. 3.1 g (10 mmol) of hydroxylammonium bis(trifluoromethylsulfonyl)amine and 23 g (10 mmol) of 1,1,1,3,3-pentafluoro-3-methoxy-2-trifluoromethyl-propane were added to 75 g of 4-methyltetrahydropyran under ice-water cooling. Subsequently, a solution of 7.1 g (30 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 25 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After about 16 hours, the mixture was cooled with ice water, and a solution of 6.1 g (26 mmol) of tert-butylimino-tris(dimethylamino)phosphorane in 20 g of 4-methyltetrahydropyran was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column. The analytical results of the obtained compound were the same as those of the product in Example 17.

[0176] In Example 19, the isolation yield of the obtained compound was not calculated, but an increase in the types and amounts of impurities is expected due to by-products that may be generated in the process of producing 1,3,3,3-tetrafluoro-1-methoxy-2-(trifluoromethyl)-1-propene in the system from 1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)-propane. Therefore, the production method of Example 17 is considered to have a higher isolation yield of the obtained product than the corresponding production method of Example 19.

[0177] Example 20 Preparation of 5-(1-benzimidazolyl)-3-methoxy-4-trifluoromethylisoxazole Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride and 3.1 g (14 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 45 g of methanol. Subsequently, a solution of 2.9 g (28 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 1.7 g (14 mmol) of benzimidazole and 4.4 g (42 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.6 g of the compound represented by the following formula (31). The isolated yield of the obtained compound was 15%.

[0178]

[0179] The analytical results were as follows: Mass spectrum (APCI, m / z): 283 ([M] ＋ ) １ H-NMR (400MHz, CDCl ３ ) δppm: 8.21 (s, 1H), 7.90 (d, 1H), 7.70 (d, 1H), 7.46 (dd, 2H), 4.16 (m, 3H)

[0180] Example 21 Preparation of 3-methoxy-5-(N-methoxymethylamino)-4-trifluoromethylisoxazole Under ice-water cooling, 1.0 g (14 mmol) of hydroxylamine hydrochloride and 3.1 g (14 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 45 g of methanol. Subsequently, a solution of 2.9 g (28 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After approximately 16 hours, the mixture was cooled with ice-water, and a solution of 1.4 g (14 mmol) of N-methoxymethylamine hydrochloride and 5.8 g (56 mmol) of triethylamine in 20 g of methanol was added dropwise so that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After about 8 hours, the reaction mixture was dissolved in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=7:3) and purified using a silica gel column to obtain 0.3 g of the compound represented by the following formula (32). The isolated yield of the obtained compound was 8%.

[0181]

[0182] The analytical results were as follows: Mass spectrum (APCI, m / z): 226 ([M] ＋ ) １ H-NMR (400MHz, CDCl ３ ) δppm: 3.98 (s, 3H), 3.74 (s, 3H), 3.21 (s, 3H)

[0183] Example 22 Preparation of 5-[(N-diphenylmethylene)amino]-3-methoxy-4-trifluoromethylisoxazole 0.5 g (7.3 mmol) of hydroxylamine hydrochloride and 1.5 g (7.1 mmol) of 1,3,3,3-tetrafluoro-1-methoxy-2-trifluoromethyl-1-propene were added to 14 ml of methanol. Subsequently, after cooling to 0°C, 1.5 g (14.6 mmol) of triethylamine was added dropwise, and the temperature was raised to room temperature. After approximately 19 hours, the mixture was cooled to 0°C, and 1.3 g (7.2 mmol) of benzophenone imine and 2.2 g (21.8 mmol) of triethylamine were added dropwise, and the temperature was raised to 60°C. After approximately 7 hours, the mixture was cooled and purified with a silica gel column to obtain a trace amount of the compound represented by the following formula (33).

[0184]

[0185] The analytical results were as follows: Mass spectrum (APCI, m / z): 346 ([M] ＋ )

Claims

1. A fluorine-containing isoxazole compound represented by the following general formula (A): (In the above general formula (A), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.

2. The fluorine-containing isoxazole compound according to claim 1, which is a compound represented by the following general formula (1), (2), (3) or (4): (In the above general formula (1), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ wherein n is an integer of 1 to 20; (In the above general formula (2), R represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ wherein n is an integer of 1 to 20; (In the above general formula (3), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ wherein n is an integer of 1 to 20; or (In the above general formula (4), R' represents a substituted or unsubstituted hydrocarbon having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

3. A method for producing a fluorine-containing isoxazole compound, comprising the steps of: (I) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with hydroxylamine or a salt thereof, and, optionally, a compound represented by the following general formula (5) or a salt thereof, or (II) reacting a fluorine-containing compound selected from fluorine-containing carbonyl compounds, fluoroisobutene derivatives, and fluoroisobutane derivatives with an amine salt or an amine compound, and, optionally, a compound represented by the following general formula (5) or a salt thereof, to synthesize a fluorine-containing isoxazole compound represented by the following general formula (A): (In the above general formulas (A) and (5), R represents a hydrogen atom or a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA ３ -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A ３ each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; Y １ and Y ２ each independently represents N or O and is different from each other.

4. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (6) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (6) and (7), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ５ A ６ , -NA ５ A ６ , -NA ５ (OA ６ ), or -NA ７ -NA ５ A ６ represents, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and the wavy bond represents a single bond that represents either (E) or (Z) stereoisomerism.

5. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (8), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (8), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents A １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

6. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (9) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then further reacting the resulting reaction product with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (9), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Z is -OA ５ , -O-NA ６ A ７ , -NA ５ A ６ , -NA ５ (OA ６ ) or -NA ７ -NA ５ A ６ represents, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; ５ , A ６ and A ７ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

7. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (10), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

8. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting it with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting it with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1): (In the above general formulas (1), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

9. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (1). (In the above general formulas (1), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

10. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (13) with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2) and (13), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, and X represents -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ where n is an integer of 1 to 20, and the wavy bond represents a single bond that represents the (E) or (Z) stereoisomerism.

11. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluorine-containing carbonyl compound represented by the following general formula (14), an amine salt or an amine compound, and optionally a compound represented by the following general formula (5) or a salt thereof, to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (14), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

12. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (15) with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (15), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a hydrogen atom, a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, or a heterocycle; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

13. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (10), R represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

14. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting it with an alcohol, reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base, and then reacting it with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2): (In the above general formulas (2), (5) and (11), R and R′ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

15. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of: carbonylating a compound obtained by an elimination reaction of a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile; further reacting the resulting reaction product with an alcohol; reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof in the presence of a base; and then reacting the resulting reaction product with an amine salt or an amine compound to obtain a fluorine-containing isoxazole compound represented by the following general formula (2). (In the above general formulas (2), (5) and (12), R and R′ each independently represent a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

16. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of reacting a fluorine-containing carbonyl compound represented by the following general formula (10) with a hydroxylamine represented by the following general formula (7) or a salt thereof, and further reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3): (In the above general formulas (3), (5) and (10), X is a halogen atom, —OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group or heterocycle having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; W ＋ represents an ammonium cation, an imidazolium cation, a pyridinium cation, a quinuclidium cation, or a phosphonium cation.

17. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of carbonylating a fluoroisobutene derivative represented by the following general formula (11) in the presence of a nucleophile, further reacting the fluoroisobutene derivative with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3). (In the above general formulas (3), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

18. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising the steps of carbonylating a fluoroisobutane derivative represented by the following general formula (12) in the presence of a nucleophile, further reacting it with a hydroxylamine represented by the following general formula (7) or a salt thereof, and then reacting the resulting reaction product with a compound represented by the following general formula (5) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (3). (In the above general formulas (3), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

19. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4): (In the above general formulas (4), (5) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ (OA ２ ), -NA １ A ２ , -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ and n is an integer of 1 to 20.

20. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutene derivative represented by the following general formula (11) with a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4-1): (In the above general formulas (4-1) and (11), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.) 21. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12), a compound represented by the following general formula (5) or a salt thereof, and a hydroxylamine represented by the following general formula (7) or a salt thereof to obtain a fluorine-containing isoxazole compound represented by the following general formula (4): (In the above general formulas (4), (5) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, X represents a halogen atom, -OA １ , -O-NA １ A ２ , -NA １ A ２ , -NA １ (OA ２ ), -NA 3 -NA １ A ２ , -NA ４ or a heterocycle, Y represents a halogen atom, —OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; １ , A ２ and A 3 each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms; ４ Is = C ｎ H ２ｎ n is an integer of 1 to 20; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.

22. A method for producing a fluorine-containing isoxazole compound according to claim 3, comprising a step of reacting a fluoroisobutane derivative represented by the following general formula (12) with a hydroxylamine represented by the following general formula (7) to obtain a fluorine-containing isoxazole compound represented by the following general formula (4-1): (In the above general formulas (4-1) and (12), R' represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms, Y represents a halogen atom, -OB １ , -SO ｍ B １ or -NB １ B ２ m is an integer of 0 to 3; B １ and B ２ each independently represents a substituted or unsubstituted hydrocarbon group having 1 to 12 carbon atoms.