Trifluoromethanesulfonylating agent composition, and method for producing trifluoromethanesulfonyloxy compound or trifluoromethanesulfonyl compound

Abstract

The present disclosure provides: a trifluoromethanesulfonylation agent composition comprising a compound represented by general formula (1) or (11) as described in the specification; and a method for producing a trifluoromethanesulfonyloxy compound or a method for producing a trifluoromethanesulfonyl compound by reacting the trifluoromethanesulfonylating agent composition with a compound represented by general formula (2) described in the description or a specific substrate.

Description

Technical Field

[0001] The present disclosure relates to a trifluoromethanesulfonylating agent composition capable of trifluoromethanesulfonylating a substrate containing a functional group such as a phenolic hydroxyl group, and a method for producing a trifluoromethanesulfonyloxy compound or a trifluoromethanesulfonyl compound using the same. Background Art

[0002] In the synthesis of pharmaceutical raw materials or intermediates, substrates having various functional groups are trifluoromethanesulfonated.

[0003] Triflation of phenolic hydroxyl groups is an important reaction in the synthesis of bulk drugs or intermediates of pharmaceuticals. Examples thereof include: a method of reacting a substrate having a phenolic hydroxyl group with trifluoromethanesulfonic anhydride (Patent Document 1, Non-Patent Document 1, Non-Patent Document 2); a method of reacting a substrate having a phenolic hydroxyl group with trifluoromethanesulfonyl fluoride (Patent Document 2); a method of reacting a substrate having a phenolic hydroxyl group with trifluoromethanesulfonyl chloride (Patent Document 3); a method of reacting a substrate having a phenolic hydroxyl group with N-phenyltrifluoromethanesulfonimide (Patent Document 4); a method of reacting a substrate having a phenolic hydroxyl group with 5-chloro-2-pyridyltrifluoromethanesulfonimide (Patent Document 5); a method of reacting a substrate having a phenolic hydroxyl group with 4-nitrophenyl trifluoromethanesulfonate (Non-Patent Document 3); a method of reacting a substrate having a phenolic hydroxyl group with 2-pyridyltrifluoromethanesulfonimide (Patent Document 6).

[0004] In addition to substrates with phenolic hydroxyl groups, triflates of ketones, primary or secondary amines were also performed.

[0005] As the triflation reaction, for example, Non-Patent Documents 4 and 5 describe a method of reacting a metal enolate, a substrate having a phenolic hydroxyl group or a secondary amine, and N-phenyltrifluoromethanesulfonimide.

[0006] In addition, a method of reacting a metal enolate with N-2-pyridyl trifluoromethanesulfonimide or a metal enolate with N-5-chloro-2-pyridyl trifluoromethanesulfonimide is described in Non-Patent Document 6. A method of reacting a ketone with trifluoromethanesulfonic anhydride is described in Non-Patent Documents 7 and 8.

[0007] Prior art literature

[0008] Patent Literature

[0009] Patent Document 1: Chinese Patent Application Publication No. 104230960

[0010] Patent Document 2: Japanese Patent Application Publication No. 2002-128752

[0011] Patent Document 3: International Publication No. 2011 / 095625

[0012] Patent Document 4: International Publication No. 2014 / 190271

[0013] Patent Document 5: International Publication No. 2013 / 044092

[0014] Patent Document 6: International Publication No. 2007 / 073503

[0015] Non-patent literature

[0016] Non-patent literature 1: P. Kancharla. et al, Journal of Medicial Chemistry, 2020, 63, 6179-6202.

[0017] Non-patent literature 2: D.Xi.et al, European Journal of Medicinal Chemistry.2019,178,802-817.

[0018] Non-patent document 3: M. Lesperance. et al., Steroids. 2018, 140, 104-113

[0019] Non-patent document 4: JB; Hendrickson. et al, Tetrahedron Letters, 1973, 46, 4607-4610.

[0020] Non-patent literature 5: JEMcMurry et al, Tetrahedron Letters, 1983, 10, 979-982.

[0021] Non-patent document 6: dL Comins. et al, Tetrahedron Letters, 1992, 42, 6299-6302.

[0022] Non-patent literature 7: M. Tranchant. et al, Tetrahedron, 2002, 58, 8425-8432.

[0023] Non-patent literature 8: PJ Stang. et al, Synthesis. 1980, 4, 283-284. Summary of the invention

[0024] Problem that the invention aims to solve

[0025] However, there is still room for further research on triflation agents from the perspectives of economic efficiency and reduction of by-products.

[0026] The present disclosure is completed in view of this situation. The subject of the present disclosure is to provide a trifluoromethanesulfonylating agent composition capable of trifluoromethanesulfonylating a substrate having a functional group such as a phenolic hydroxyl group. In addition, the subject of the present invention is also to provide an efficient and industrially feasible method for producing a trifluoromethanesulfonyloxy compound or a trifluoromethanesulfonyl compound.

[0027] Solutions for solving problems

[0028] Therefore, the present inventors conducted intensive research in view of the above-mentioned problems. As a result, it was found that the trifluoromethanesulfonylating agent composition containing a specific trifluoromethanesulfonylating agent disclosed in the present invention can suppress the generation of by-products and can trifluoromethanesulfonate a substrate having a functional group such as a phenolic hydroxyl group. It was also found that the trifluoromethanesulfonyloxy compound can be separated from the reaction solution after the trifluoromethanesulfonylation reaction only by a conventional post-treatment operation, and the trifluoromethanesulfonyloxy compound or the trifluoromethanesulfonyl compound can be efficiently obtained.

[0029] That is, the present disclosure provides the inventions described in the following [1] to

[16] . [1]

[0031] A trifluoromethanesulfonylating agent composition comprises a compound represented by the following general formula (1) or (11).

[0032]

[0033] (In general formulas (1) and (11), R 1 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0034] R 2 is a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms,

[0035] X is a nitrogen atom or C(R 3 ), Y is a nitrogen atom or C(R 4 ),

[0036] R 3 is a hydrogen atom, a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms,

[0037] R 4is a hydrogen atom, a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms,

[0038] R 2 With R 3 optionally bonded to form a ring, R 2 With R 4 optionally bonded to form a ring,

[0039] n is an integer of 1 to 3.

[0040] There are multiple R 2 In the case of R 2 Optionally the same or different, there are multiple R 3 In the case of R 3 They may be the same or different.

[0041] In the general formula (11), R 5 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0042] Z - is an anion.) [2]

[0044] The trifluoromethanesulfonylating agent composition according to [1], comprising:

[0045] The compound represented by the above general formula (1), and

[0046] Any base selected from the group consisting of aliphatic organic bases, heterocyclic group-containing organic bases and inorganic bases. [3]

[0048] The trifluoromethanesulfonylating agent composition according to [2], wherein in the general formula (1), X is C(R 3 ), R 1 , R 2 and R 3 are each independently a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or an isopropyl group. [4]

[0050] The triflation agent composition according to [2] or [3], wherein the organic base is selected from the group consisting of secondary amines, tertiary amines, alkoxides, and organic bases containing a heterocyclic group having a nitrogen atom and having 4 or more carbon atoms. [5]

[0052] The triflation agent composition according to any one of [2] to [4], wherein the inorganic base is selected from the group consisting of potassium salts and sodium salts. [6]

[0054] The trifluoromethanesulfonylating agent composition according to any one of [2] to [5], wherein the base is any one selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium methoxide, lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, triethylamine, tri-n-propylamine, tributylamine, diisopropylethylamine, N,N-diethylcyclohexylamine, 1,8-diazabicyclo[5.4.0]undecene, and 1,5-diazabicyclo[4.3.0]nonene. [7]

[0056] A method for producing a trifluoromethanesulfonyloxy compound, wherein:

[0057] The trifluoromethanesulfonylating agent composition described in any one of [2] to [6] is reacted with an aromatic hydroxy compound represented by the general formula (2).

[0058] Ar-OH (2)

[0059] (In the general formula (2), Ar represents an aromatic ring group or a substituted aromatic ring group.) [8]

[0061] The method for producing a trifluoromethanesulfonyloxy compound according to [7], wherein in the general formula (2), Ar represents an aromatic ring group, and the aromatic ring group is an aromatic heterocyclic group. [9]

[0063] The method for producing a trifluoromethanesulfonyloxy compound according to [7], wherein in the general formula (2), Ar represents a substituted aromatic ring group, and the substituent possessed by the substituted aromatic ring group is a lower alkyl group, a lower alkoxycarbonyl group, a lower alkyl group, a β-D-pyranoglucopyranoside group, an amino group, a lower alkylamino group or a hydroxyl group.

[10]

[0065] The method for producing a trifluoromethanesulfonyloxy compound according to any one of [7] to [9], wherein the reaction is carried out at a reaction temperature of 150° C. or less.

[11]

[0067] The method for producing a trifluoromethanesulfonyloxy compound according to any one of [7] to

[10] , wherein the reaction mixture after completion of the reaction is post-treated with an acidic aqueous solution.

[12]

[0069] The triflation agent composition according to [1], wherein the compound represented by the general formula (11) is a compound represented by the following general formula (11a).

[0070]

[0071] (In general formula (11a), R 11 , R 12 and R 15 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0072] Xa is a nitrogen atom or C(R 13 ),

[0073] R 13 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0074] R 12 With R 13 They are optionally bonded to form a ring.

[0075] Z - is an anion.)

[13]

[0077] The trifluoromethanesulfonylating agent composition according to

[12] , wherein Z in the general formula (11a) - is a trifluoromethanesulfonate anion, a fluoromethanesulfonate anion, a methanesulfonate anion or a sulfonate anion.

[14]

[0079] The trifluoromethanesulfonylating agent composition according to

[12] or

[13] , wherein Xa in the general formula (11a) is C(R 13 ).

[15]

[0081] The trifluoromethanesulfonylating agent composition according to any one of

[12] to

[14] , wherein Xa in the general formula (11a) is C(R 13 ), R 11 , R 12 , R 13 and R 15 are each independently a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or an isopropyl group.

[16]

[0083] A method for producing a trifluoromethanesulfonyl compound, comprising reacting the trifluoromethanesulfonylating agent composition according to any one of

[12] to

[15] with at least one substrate selected from the group consisting of a compound having a phenolic hydroxyl group, a compound having an alcoholic hydroxyl group, a ketone, a primary amine and a secondary amine.

[0084] Effects of the Invention

[0085] According to the present disclosure, a triflation agent composition capable of triflation of a substrate having a functional group such as a phenolic hydroxyl group can be provided. In addition, an industrially feasible and efficient method for producing a triflation agent composition or a triflation agent compound can be provided. DETAILED DESCRIPTION

[0086] Hereinafter, the present disclosure will be described in detail. Hereinafter, embodiments of the present disclosure will be described, but the present invention is not limited to the following embodiments, and can be appropriately implemented according to the general knowledge of those skilled in the art within the scope not impairing the gist of the present disclosure.

[0087] <Trifluoromethanesulfonylating agent composition>

[0088] (Trifluoromethanesulfonylating agent)

[0089] The triflation agent composition of the present disclosure (hereinafter also referred to as the composition of the present disclosure) contains a compound represented by the following general formula (1) or (11) as a triflation agent.

[0090]

[0091] In the general formulas (1) and (11), R 1 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0092] R 2 is a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms,

[0093] X is a nitrogen atom or C(R 3 ), Y is a nitrogen atom or C(R 4 ),

[0094] R 3 is a hydrogen atom, a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms,

[0095] R 4 is a hydrogen atom, a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms,

[0096] R 2 With R 3 optionally bonded to form a ring, R 2 With R 4 optionally bonded to form a ring,

[0097] n is an integer of 1 to 3.

[0098] There are multiple R 2 In the case of R 2 Optionally the same or different, there are multiple R 3 In the case of R 3 They may be the same or different.

[0099] In the general formula (11), R 5 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0100] Z - It is an anion.

[0101] In the general formulas (1) and (11), R 1 It represents a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms.

[0102] Examples of the linear alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, and an n-hexyl group.

[0103] Examples of the branched alkyl group having 3 to 6 carbon atoms include isopropyl, isobutyl, sec-butyl, and tert-butyl.

[0104] Among them, from the perspective of easy synthesis, R 1 Preferred is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group or an isopropyl group.

[0105] In the general formulas (1) and (11), R 2 represents a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms. 2 In the case of R 2 They may be the same or different.

[0106] Examples of the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms include a linear alkyl group having 1 to 6 carbon atoms, a linear alkenyl group having 2 to 6 carbon atoms, and a linear alkynyl group having 2 to 6 carbon atoms.

[0107] Examples of the linear alkyl group having 1 to 6 carbon atoms include: 1 Examples of the straight-chain alkyl group having 1 to 6 carbon atoms are described below.

[0108] Examples of the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms include a branched alkyl group having 3 to 6 carbon atoms, a branched alkenyl group having 3 to 6 carbon atoms, and a branched alkynyl group having 3 to 6 carbon atoms.

[0109] Examples of the branched alkyl group having 3 to 6 carbon atoms include: 1 The examples described are those of a branched alkyl group having 3 to 6 carbon atoms.

[0110] Examples of the aromatic hydrocarbon group having 6 to 14 carbon atoms include a phenyl group, a naphthyl group, an anthracenyl group, and the like.

[0111] Examples of the aromatic heterocyclic group having 6 to 14 carbon atoms include a pyrrolyl group, a pyrazinyl group, a pyrimidinyl group, and a pyridazinyl group.

[0112] R 2 It is preferably a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, or a nitro group; it is preferably a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms.

[0113] R 2 Preferred is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group or a nitro group; more preferred is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group or an isopropyl group.

[0114] In the general formulas (1) and (11), X is a nitrogen atom or C(R 3 ), Y is a nitrogen atom or C(R 4 ).

[0115] R 3 represents a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms. 3 In the case of R 3 They may be the same or different.

[0116] Examples of the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 6 to 14 carbon atoms include: 2 Examples include a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, and an aromatic heterocyclic group having 6 to 14 carbon atoms.

[0117] R 3 It is preferably a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms; and more preferably a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

[0118] R 4 represents a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms. 4 In the case of R 4They may be the same or different.

[0119] Examples of the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 6 to 14 carbon atoms include: 2 Examples include a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, and an aromatic heterocyclic group having 6 to 14 carbon atoms.

[0120] R 4 It is preferably a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms; and more preferably a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

[0121] In the general formulae (1) and (11), preferably X is C(R 3 ), Y is a nitrogen atom.

[0122] n is an integer of 1 to 3. Preferably n is 1.

[0123] R 2 With R 3 They are optionally bonded to form a ring. 2 With R 3 The ring formed by bonding is not particularly limited, and examples thereof include an aromatic hydrocarbon ring having 6 to 14 carbon atoms (eg, a naphthalene ring and an anthracene ring) and an aromatic heterocyclic ring having 6 to 14 carbon atoms.

[0124] R 2 With R 4 They are optionally bonded to form a ring. 2 With R 4 The ring formed by bonding is not particularly limited, and examples thereof include an aromatic hydrocarbon ring having 6 to 14 carbon atoms (eg, a naphthalene ring and an anthracene ring) and an aromatic heterocyclic ring having 6 to 14 carbon atoms.

[0125] In the general formula (1), preferably X is C(R 3 ), R 1 , R 2 and R 3 are each independently a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or an isopropyl group.

[0126] In the general formula (11), R 5 It is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms.

[0127] As R 5 As the linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms, R 1The same applies to the examples described above of the linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms, and the preferred examples are also the same.

[0128] R 5 It is preferably bonded to X or Y, and more preferably bonded to Y.

[0129] As a preferred method, R 5 It bonds to the nitrogen atom in X to form a cation portion.

[0130] In addition, as a preferred embodiment, R 5 It bonds to the nitrogen atom in Y to form a cation portion.

[0131] In the general formula (11), Z - Represents an anion.

[0132] Z - It is preferably an anion of a strong acid or a superacid, preferably a tetrafluoroborate anion, a hexafluorophosphate anion, a hexafluoroantimonate anion, a fluorosulfonate anion, a trifluoroacetate anion, a trifluoromethanesulfonate anion, a fluoromethanesulfonate anion, a methanesulfonate anion, a toluenesulfonate anion or a sulfonate anion; more preferably a trifluoromethanesulfonate anion, a fluoromethanesulfonate anion, a methanesulfonate anion, a toluenesulfonate anion or a sulfonate anion; further preferably a trifluoromethanesulfonate anion.

[0133] The compound represented by the general formula (11) is preferably a compound represented by the following general formula (11a).

[0134]

[0135] In the general formula (11a), R 11 , R 12 and R 15 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0136] Xa is a nitrogen atom or C(R 13 ),

[0137] R 13 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms,

[0138] R 12 With R 13 They are optionally bonded to form a ring.

[0139] Z - It is an anion.

[0140] For R 11 , R 12 and R 15As the linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms, R in the general formula (11) can be exemplified as 1 , R 2 and R 5 Examples of the straight-chain alkyl group having 1 to 6 carbon atoms and the branched-chain alkyl group having 3 to 6 carbon atoms are described.

[0141] In the general formula (11a), Xa is a nitrogen atom or C(R 13 ), preferably C(R 13 ).

[0142] For R 13 As the linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms, R in the general formula (11) can be exemplified as 3 Examples of the straight-chain alkyl group having 1 to 6 carbon atoms and the branched-chain alkyl group having 3 to 6 carbon atoms are described.

[0143] From the viewpoint of easy synthesis, it is preferred that Xa in the general formula (11a) is C(R 13 ), R 11 , R 12 , R 13 and R 15 Each is independently a hydrogen atom, a methyl group, an ethyl group, an n-propyl group or an isopropyl group; a hydrogen atom or a methyl group is particularly preferred.

[0144] Z in the general formula (11a) - With Z in the general formula (11) - The meanings are the same, and the preferred examples are also the same.

[0145] Although the compounds represented by the general formula (1) are exemplified below, the compounds are not limited to these.

[0146]

[0147] Although the compounds represented by the general formula (11) are exemplified below, the compounds are not limited to these.

[0148]

[0149]

[0150] · Method 1

[0151] By using a triflation agent composition containing a compound represented by the above general formula (1) or (11), a substrate having a phenolic hydroxyl group or the like can be triflated. As one preferred embodiment of the present disclosure, there can be mentioned a triflation agent composition comprising: a compound represented by the above general formula (1) and any base selected from the group consisting of an aliphatic organic base, a heterocyclic group-containing organic base and an inorganic base.

[0152] By using a trifluoromethanesulfonylating agent composition (hereinafter also referred to as the first trifluoromethanesulfonylating agent composition or simply referred to as the first composition) comprising a compound represented by the general formula (1) and a specific base, the generation of by-products can be suppressed, and the phenolic hydroxyl group can be selectively trifluoromethanesulfonated. In addition, the trifluoromethanesulfonyloxy compound can be separated from the reaction solution after the trifluoromethanesulfonylation reaction only by a conventional post-treatment operation, thereby obtaining the trifluoromethanesulfonyloxy compound in an industrially feasible and efficient manner.

[0153] In addition, in this specification, the triflation agent "selectively reacts" with respect to the phenolic hydroxyl group means that the triflation reaction preferentially proceeds with respect to the phenolic hydroxyl group.

[0154] The compound represented by the general formula (1) is contained in an amount of preferably 80% or more, more preferably 90% or more, based on the total mass of the first composition.

[0155] (Alkali)

[0156] The first triflation agent composition of the present disclosure preferably contains a base.

[0157] Examples of the base used in the first triflation agent composition include any base selected from the group consisting of aliphatic organic bases, heterocyclic group-containing organic bases, and inorganic bases.

[0158] The organic base is preferably a base selected from the group consisting of secondary amines, tertiary amines, alkoxides, and organic bases containing a heterocyclic group having a nitrogen atom and having 4 or more carbon atoms.

[0159] The aliphatic organic base is an organic base having an aliphatic hydrocarbon group and having no aromatic group.

[0160] Specifically, secondary amines, tertiary amines or alkoxides are preferred, and examples thereof include lithium methoxide, lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, dipropylamine, diisobutylamine, trimethylamine, triethylamine, tri-n-propylamine, tributylamine, diisopropylethylamine, and N,N-diethylcyclohexylamine.

[0161] The heterocyclic group-containing organic base is preferably a compound having a heterocyclic group having 4 or more carbon atoms, and more preferably a compound containing a heterocyclic group having a nitrogen atom and having 4 or more carbon atoms.

[0162] Specific examples thereof include 1,8-diazabicyclo[5.4.0]undecene, 1,5-diazabicyclo[4.3.0]nonene, pyridine, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 2,3,4-trimethylpyridine, 2,4,5-trimethylpyridine, 2,5,6-trimethylpyridine, 2,4,6-trimethylpyridine, 3,4,5-trimethylpyridine, and 3,5,6-trimethylpyridine.

[0163] The inorganic base is preferably a base selected from the group consisting of sodium salts and potassium salts, and examples thereof include sodium carbonate, potassium carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate.

[0164] In addition, alkali metal hydrides are also preferred, and examples thereof include sodium hydride and potassium hydride.

[0165] The base is preferably any one selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium methoxide, lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, triethylamine, tri-n-propylamine, tributylamine, diisopropylethylamine, N,N-diethylcyclohexylamine, 1,8-diazabicyclo[5.4.0]undecene and 1,5-diazabicyclo[4.3.0]nonene.

[0166] Among them, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium tert-butoxide or potassium tert-butoxide are preferred; potassium carbonate, potassium bicarbonate or potassium tert-butoxide are particularly preferred. These bases can be used alone or in combination.

[0167] In addition, as another preferred embodiment, when the base is an organic base, the organic base is preferably any one selected from the group consisting of trimethylamine, triethylamine, diisopropylethylamine, tri-n-propylamine, pyridine, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 2,3,4-trimethylpyridine, 2,4,5-trimethylpyridine, 2,5,6-trimethylpyridine, 2,4,6-trimethylpyridine, 3,4,5-trimethylpyridine and 3,5,6-trimethylpyridine.

[0168] These bases may be used alone or in combination.

[0169] The amount of the base used is not particularly limited, but is usually preferably 0.01 to 20 mol, and more preferably 0.05 to 5 mol, based on 1 mol of the trifluoromethanesulfonyl compound described below.

[0170] In addition, the first composition of the present disclosure may further contain a solvent.

[0171] The solvent is not particularly limited as long as it can dissolve the compound represented by the general formula (1) and the base, and examples thereof include the reaction solvent for trifluoromethanesulfonylation described later.

[0172] In addition, the first composition of the present disclosure may or may not contain a solvent.

[0173] <Method for producing trifluoromethanesulfonyloxy compound>

[0174] The method for producing a trifluoromethanesulfonyloxy compound using the first composition of the present disclosure (hereinafter also referred to as the first production method) includes the step of reacting the first trifluoromethanesulfonylating agent composition with a compound represented by the following general formula (2).

[0175] (Trifluoromethanesulfonyl compound)

[0176] The compound to be trifluoromethanesulfonated with the first trifluoromethanesulfonylating agent composition (hereinafter also referred to as the trifluoromethanesulfonated compound) is an aromatic hydroxy compound represented by the following general formula (2).

[0177] General formula (2):

[0178] Ar-OH (2) In the general formula (2), Ar represents an aromatic ring group or a substituted aromatic ring group.

[0179] Ar of the aromatic ring hydroxy compound represented by the general formula (2) represents an aromatic ring group or a substituted aromatic ring group.

[0180] The aromatic ring group is not particularly limited and may be either a monocyclic ring or a polycyclic ring, and is preferably an aromatic ring group having 1 to 18 carbon atoms, for example, aromatic hydrocarbon groups such as phenyl, naphthyl and anthracenyl; aromatic heterocyclic groups containing heteroatoms such as nitrogen atoms, oxygen atoms or sulfur atoms such as pyrrolyl (including nitrogen protected bodies), pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazine, furanyl, thienyl, indolyl (including nitrogen protected bodies), indazolyl, quinolyl, carbazolyl, pyrrolopyridinyl, benzofuranyl and benzothienyl.

[0181] In the above general formula (2), Ar represents an aromatic ring group, and the aromatic ring group is preferably an aromatic heterocyclic group.

[0182] The substituted aromatic ring group has substituents in any number and in any combination on any carbon atom or nitrogen atom of the aforementioned aromatic ring group. The substituents are: halogen atoms of fluorine, chlorine, bromine and iodine; lower alkyl groups such as methyl, ethyl and propyl; lower unsaturated groups such as vinyl, allyl and propargyl; lower haloalkyl groups such as fluoromethyl, chloromethyl and bromomethyl; lower alkoxy groups such as C(CF3)2OH (including hydroxyl protection bodies), methoxy, ethoxy and propoxy; lower haloalkoxy groups such as fluoromethoxy, chloromethoxy and bromomethoxy; lower acyloxy groups such as formyloxy, acetoxy, propionyloxy and butyryloxy; cyano, methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl, etc. lower alkoxycarbonyl; lower alkoxycarbonyl lower alkyl such as methoxycarbonylmethyl, ethoxycarbonylethyl and propoxycarbonylpropyl; aromatic ring groups such as β-D-pyranoglucopyranoside, phenyl, naphthyl, anthracenyl, pyrrolyl (including nitrogen protection), pyridyl, furanyl, thienyl, indolyl (including nitrogen protection), quinolyl, benzofuranyl and benzothienyl; carboxyl protection, amino, amino protection, lower alkylamino, lower alkylamino lower alkyl, hydroxyl, hydroxyl protection, and X'-Ar'-OH group, etc. These substituents may be further substituted, for example, they may be further substituted by the substituents of the aforementioned "substituents".

[0183] In the above general formula (2), Ar represents a substituted aromatic ring group, and the substituent of the substituted aromatic ring group is preferably a lower alkyl group, a lower alkoxycarbonyl group, a lower alkyl group, a β-D-pyranoglucopyranoside group, an amino group, a lower alkylamino group or a hydroxyl group.

[0184] X' of the X'-Ar'-OH group represents a C(CH3)2 group, a C(CF3)2 group, an oxygen atom, a nitrogen atom (including nitrogen protection bodies), a sulfur atom, an SO group or an SO2 group, and Ar' represents a phenylene group or a substituted phenylene group. The substitution position of the phenylene group is the 2nd, 3rd or 4th position relative to the hydroxyl group. The substituent of the substituted phenylene group is the same as the substituent of the aforementioned substituted aromatic ring group. Specific examples of the aromatic hydroxy compound represented by the general formula (2) formed by substitution of the X'-Ar'-OH group include the following compounds.

[0185]

[0186] It should be noted that, in this specification, the term "lower" refers to a straight chain or branched chain or ring having 1 to 6 carbon atoms (when the carbon number is 3 or more). In addition, the aromatic ring group of the aforementioned "substituent" may also be substituted by a halogen atom, a lower alkyl group, a lower unsaturated group, a lower haloalkyl group, a C(CF3)2OH group (including a hydroxyl protective body), a lower alkoxy group, a lower haloalkoxy group, a formyloxy group, a lower acyloxy group, a cyano group, a lower alkoxycarbonyl group, a lower alkoxycarbonyl lower alkyl group, a carboxyl protective body, an amino protective body, a hydroxyl group, a hydroxyl protective body, and an X'-Ar'-OH group. Furthermore, the protective groups of pyrrolyl, indolyl, hydroxyl, carboxyl, and amino are the protective groups described in Protective Groups in Organic Synthesis, Third Edition, 1999, John Wiley & Sons, Inc., etc. Among them, aromatic ring groups and substituted aromatic ring groups that do not include "hydroxyl group", "aromatic ring group" and "X'-Ar'-OH group" as substituents are preferred; aromatic hydrocarbon groups and substituted aromatic hydrocarbon groups (aromatic hydrocarbon groups having substituents) that do not include "hydroxyl group", "aromatic ring group" and "X'-Ar'-OH group" as substituents are particularly preferred. Depending on the reaction conditions used, aromatic ring hydroxy compounds having multiple hydroxyl groups may be fluorinated multiple times.

[0187] As a preferred embodiment, the aromatic cyclic hydroxy compound represented by the general formula (2) has at least one substituent selected from alcoholic hydroxyl group and amino group. These substituents may be further substituted, for example, may be further substituted by the substituents of the aforementioned "substituent".

[0188] Although the compounds represented by the general formula (2) are exemplified below, the compounds are not limited to these.

[0189]

[0190] In the trifluoromethanesulfonylation reaction, the aromatic hydroxy compound represented by the general formula (2) is preferably used in an amount of 0.7 mol to 1.2 mol, more preferably 0.8 mol to 1.0 mol, based on 1.0 mol of the trifluoromethanesulfonyl compound represented by the general formula (1).

[0191] (Solvent)

[0192] The above trifluoromethanesulfonylation reaction is preferably carried out using a reaction solvent.

[0193] Examples of the reaction solvent for trifluoromethanesulfonylation include ether solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, ester solvents, amide solvents, nitrile solvents, and sulfoxide solvents.

[0194] Specific examples of these reaction solvents include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, tetrahydropyran, 1,4-dioxane, and cyclopentyl methyl ether.

[0195] Examples of the aliphatic hydrocarbon solvent include n-hexane, n-heptane, n-pentane, n-nonane, and n-decane.

[0196] Examples of the aromatic hydrocarbon solvent include toluene, xylene, mesitylene, and ethylbenzene.

[0197] Examples of the halogenated hydrocarbon solvent include dichloromethane, chloroform, and 1,2-dichloroethane.

[0198] Examples of the ester solvent include ethyl acetate, isopropyl acetate, n-butyl acetate, and γ-butyrolactone.

[0199] Examples of the amide solvent include N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone.

[0200] Examples of the nitrile solvent include acetonitrile, propionitrile, and benzonitrile.

[0201] Examples of the sulfoxide-based solvent include dimethyl sulfoxide and the like.

[0202] Among them, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, acetonitrile, propionitrile and dimethyl sulfoxide are preferred from the viewpoint of easy availability and excellent solubility of the substrate and the trifluoromethanesulfonylating agent disclosed herein; tetrahydrofuran, N,N-dimethylformamide and acetonitrile are particularly preferred. These reaction solvents can be used alone or in combination.

[0203] The amount of the reaction solvent used in the trifluoromethanesulfonylation is not particularly limited, but may be 0.05 L (liter) or more per 1 mol of the trifluoromethanesulfonyl compound, and is usually preferably 0.1 to 20 L, and more preferably 0.1 to 10 L.

[0204] (Reaction temperature)

[0205] The reaction temperature of trifluoromethanesulfonylation is not particularly limited, but is preferably 150°C or lower, more preferably -100 to 150°C, and further preferably -78 to 100°C.

[0206] (Reaction time)

[0207] The reaction time of trifluoromethanesulfonylation is not particularly limited and can be carried out in the range of 0.1 to 72 hours. It varies depending on the raw materials and reaction conditions. Therefore, it is preferred to track the progress of the reaction using analytical means such as gas chromatography, liquid chromatography, and NMR, and the time when the raw materials almost disappear is regarded as the end point.

[0208] (Post-processing operation: liquid separation)

[0209] After the above reaction, a conventional operation of organic synthesis may be performed as a post-treatment operation for isolating the trifluoromethanesulfonyloxy compound.

[0210] For example, the reaction solution after the reaction containing the trifluoromethanesulfonyloxy compound is preferably post-treated with water, an acidic aqueous solution or an alkaline aqueous solution. That is, the reaction solution after the reaction is diluted with an organic solvent, washed with water, an aqueous solution of a mineral acid (inorganic acid) or an aqueous solution of an alkali metal salt, and the reaction mixture (organic phase) is concentrated.

[0211] Examples of the organic solvent for post-treatment include ether solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, and ester solvents.

[0212] Specific examples of the organic solvent for post-treatment include diethyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, tetrahydropyran, cyclopentyl methyl ether, n-hexane, n-heptane, n-pentane, n-nonane, n-decane, toluene, xylene, mesitylene, ethylbenzene, dichloromethane, chloroform, 1,2-dichloroethane, ethyl acetate, and n-butyl acetate.

[0213] Among them, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, 2-methyltetrahydrofuran, cyclopentyl methyl ether, toluene, xylene, mesitylene, ethylbenzene, dichloromethane, chloroform, 1,2-dichloroethane, ethyl acetate, and n-butyl acetate are preferred; ethyl acetate is particularly preferred. These reaction solvents can be used alone or in combination.

[0214] The amount of the solvent used in the post-treatment is not particularly limited, but may be 0.05 L (liter) or more, and is usually preferably 0.1 to 20 L, and more preferably 0.1 to 10 L, based on 1 mol of the trifluoromethanesulfonyl compound.

[0215] Specific examples of the mineral acid for post-treatment include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and nitric acid. Among them, hydrochloric acid and sulfuric acid are preferred, and hydrochloric acid is particularly preferred.

[0216] Specific examples of the alkali metal salt for post-treatment include sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, or potassium carbonate.

[0217] The obtained trifluoromethanesulfonyloxy compound can be suitably and preferably used in, for example, a coupling reaction using a transition metal.

[0218] As described above, the trifluoromethanesulfonyloxy compound obtained by the first production method of the present disclosure can be separated from the reaction solution after the reaction by a simple post-treatment operation, so it can be industrially implemented, and as a result, the coupling reaction product can be produced more efficiently than the conventional method.

[0219] ·Method 2

[0220] Another preferred embodiment of the present disclosure is a triflation agent composition containing the compound represented by the above general formula (11).

[0221] By using a trifluoromethanesulfonylating agent composition containing a compound represented by general formula (11) (hereinafter also referred to as the second trifluoromethanesulfonylating agent composition or simply referred to as the second composition), not only a substrate having a phenolic hydroxyl group but also a wide range of substrates can be trifluoromethanesulfonated, and trifluoromethanesulfonyl compounds derived from these substrates can be simply provided under industrially feasible conditions.

[0222] The second composition of the present disclosure contains a trifluoromethanesulfonyl imidazolium salt or a trifluoromethanesulfonyl triazolium salt which is a compound represented by the general formula (11). These may be used in combination of two or more.

[0223] The compound represented by the general formula (11) is contained in an amount of preferably 80% or more, more preferably 90% or more, based on the total mass of the second composition.

[0224] The second composition of the present disclosure may further contain a base.

[0225] Examples of the base include bases that can be used for triflation described below.

[0226] In addition, the second composition of the present disclosure may or may not contain a base.

[0227] The amount of the base used is not particularly limited, but is usually preferably 0.01 to 20 mol, and more preferably 0.05 to 5 mol, based on 1 mol of the trifluoromethanesulfonyl compound described below.

[0228] In addition, the second composition of the present disclosure may further contain a solvent.

[0229] The solvent is not particularly limited as long as it dissolves the compound represented by the general formula (11) and, when the second composition contains a base, dissolves the base, and examples thereof include the reaction solvent for triflation described later.

[0230] In addition, the second composition of the present disclosure may or may not contain a solvent.

[0231] <Method for producing trifluoromethanesulfonyl compound>

[0232] The method for producing a trifluoromethanesulfonyl compound using the second composition of the present disclosure (hereinafter also referred to as the second production method) includes a step of reacting the second trifluoromethanesulfonylating agent composition with a trifluoromethanesulfonyl compound.

[0233] (Trifluoromethanesulfonyl compound)

[0234] The compound to be trifluoromethanesulfonated with the second trifluoromethanesulfonylating agent composition (hereinafter also referred to as the trifluoromethanesulfonyl compound) is preferably at least one substrate selected from the group consisting of compounds having a phenolic hydroxyl group, compounds having an alcoholic hydroxyl group, ketones, primary amines and secondary amines.

[0235] Examples of the compound having a phenolic hydroxyl group include aromatic hydroxy compounds represented by the above general formula (2).

[0236] Examples of the compound having an alcoholic hydroxyl group include alkyl alcohols having 1 to 20 carbon atoms, methyl lactate, phenethyl alcohol, and tetraacetyl-β-D-mannose.

[0237] Examples of the ketone include ethyl acetoacetate, acetylacetone, cyclohexanone, 1,3-cyclohexanedione, and ethyl 2-oxocyclohexanecarboxylate.

[0238] Examples of the primary amine include alkylamines having 1 to 20 carbon atoms, aniline, 1-phenylethylamine, and α-amino acids.

[0239] Examples of the secondary amine include alkylamines having 1 to 20 carbon atoms, methylaniline, N-methylphenylethylamine, and piperidine.

[0240] It should be noted that, for the above-mentioned trifluoromethanesulfonyl compound, not only compounds having one functional group in one molecule can be trifluoromethanesulfonated by the second trifluoromethanesulfonylating agent composition of the present disclosure, but also compounds having two or three functional groups in one molecule can be trifluoromethanesulfonated by the second trifluoromethanesulfonylating agent composition of the present disclosure. Depending on the reaction conditions used, a trifluoromethanesulfonyl compound having multiple functional groups may be trifluorosulfonated multiple times.

[0241] In the trifluoromethanesulfonylation reaction in which the trifluoromethanesulfonyl compound and the second trifluoromethanesulfonylating agent composition of the present disclosure are contacted to react to carry out trifluoromethanesulfonylation, the ratio of the trifluoromethanesulfonyl compound to the trifluoromethanesulfonylating agent (the compound represented by the general formula (11)) is preferably, expressed as a molar ratio, trifluoromethanesulfonyl compound:trifluoromethanesulfonylating agent = 1:0.5 to 1:5.0, and more preferably 1:1 to 1:3.0.

[0242] (Solvent)

[0243] The trifluoromethanesulfonylation reaction is preferably carried out using a reaction solvent.

[0244] Examples of the reaction solvent for trifluoromethanesulfonylation include ether solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, ester solvents, amide solvents, nitrile solvents, and sulfoxide solvents.

[0245] Specific examples of these reaction solvents include the specific examples described in the reaction solvent in the first production method, and the preferred examples are the same.

[0246] The amount of the reaction solvent used in the trifluoromethanesulfonylation is not particularly limited, but may be 0.05 L (liter) or more per 1 mol of the trifluoromethanesulfonyl compound, and is usually preferably 0.1 to 20 L, and more preferably 0.1 to 10 L.

[0247] (Alkali)

[0248] The above triflation reaction is preferably carried out using a base.

[0249] Examples of the base include the bases listed as the base that can be contained in the above-mentioned first composition.

[0250] As the base, triethylamine, sodium hydride, diisopropylethylamine, tributylamine, pyridine, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, and 3,5-lutidine are preferred; triethylamine and sodium hydride are more preferred.

[0251] The amount of the base used is not particularly limited, but is usually preferably 0.1 to 20 mol, particularly preferably 0.05 to 5 mol, based on 1 mol of the trifluoromethanesulfonyl compound described below.

[0252] (Reaction temperature)

[0253] The reaction temperature of trifluoromethanesulfonylation is not particularly limited, but is preferably 150°C or lower, more preferably -100 to 150°C, and further preferably -78 to 100°C.

[0254] (Reaction time)

[0255] The reaction time of trifluoromethanesulfonylation is not particularly limited and can be carried out in the range of 0.1 to 72 hours. It varies depending on the raw materials and reaction conditions. Therefore, it is preferred to track the progress of the reaction using analytical means such as gas chromatography, liquid chromatography, and NMR, and the time when the raw materials almost disappear is regarded as the end point.

[0256] (Post-processing operation: liquid separation)

[0257] After the above reaction, a conventional operation of organic synthesis may be performed as a post-treatment operation for isolating the trifluoromethanesulfonyl compound.

[0258] For example, it is preferred to post-treat the reaction solution containing the trifluoromethanesulfonyl compound after the reaction is completed with water, an acidic aqueous solution or an alkaline aqueous solution. That is, the reaction solution after the reaction is completed is diluted with an organic solvent, washed with water, an aqueous solution of a mineral acid (inorganic acid) or an aqueous solution of an alkali metal salt, and the reaction mixture (organic phase) is concentrated.

[0259] Examples of the organic solvent for post-treatment include ether solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, and ester solvents.

[0260] Specific examples of the organic solvent for post-treatment include the specific examples described for the organic solvent for post-treatment in the first production method, and preferred examples are the same. The organic solvents may be used alone or in combination.

[0261] The amount of the solvent used in the post-treatment is not particularly limited, but may be 0.05 L (liter) or more, and is usually preferably 0.1 to 20 L, and more preferably 0.1 to 10 L, based on 1 mol of the trifluoromethanesulfonyl compound.

[0262] Specific examples of the mineral acid and alkali metal salt to be post-treated include the specific examples described for the mineral acid and alkali metal salt to be post-treated in the first production method, and preferred examples are the same.

[0263] As described above, the trifluoromethanesulfonyl compound obtained by the second production method of the present disclosure can be separated from the reaction solution after the reaction is completed only by a simple post-treatment operation, and can be industrially implemented and efficiently produced.

[0264] Example

[0265] Hereinafter, the present disclosure will be described in detail by way of examples, but the present disclosure is not limited to these examples. Here, in Examples 1 to 22 and 28 to 35, the yield (%) refers to the yield obtained by nuclear magnetic resonance spectroscopy. 19 The value obtained by F-NMR measurement.

[0266] In the following, Synthesis Examples 1 to 3 and Examples 1 to 27 correspond to the first embodiment using a triflation agent composition comprising a compound represented by the above general formula (1) and a specific base. In addition, Synthesis Examples 4 to 7 and Examples 28 to 35 correspond to the second embodiment using a triflation agent composition comprising a compound represented by the above general formula (11).

[0267] (Synthesis example 1)

[0268] Take 5.0g of imidazole (73mmol, 1.0eq. = molar equivalent ratio, the same below), 23.5g of trifluoromethanesulfonyl chloride (139mmol, 1.9eq.), 15.6g of sodium carbonate (122mmol, 2.0eq.) and 73mL of acetonitrile as a reaction solvent, add them into a 200mL three-necked flask with a stirrer. Then, stir at room temperature (about 25°C, the same below) for 16 hours. The reaction solution is concentrated to a small amount and then 1 As a result of H-NMR analysis, the signal derived from imidazole completely disappeared, and a signal derived from 1-trifluoromethanesulfonyl imidazole was newly observed.

[0269] The reaction liquid was filtered through diatomaceous earth (Celite, registered trademark = diatomaceous earth calcined with sodium carbonate, the same below) to remove insoluble matter to obtain a filtrate, and acetonitrile was removed from the filtrate to obtain 9.7 g of 1-trifluoromethanesulfonyl imidazole.

[0270] [Physical property values]

[0271] 1-Trifluoromethanesulfonyl imidazole;

[0272] 1 H-NMR (400MHz, CD3CN) δ (ppm): 8.15 (1H, s), 7.56 (1H, s), 7.29 (1H, s)

[0273] 19 F-NMR (373MHz, CD3CN) δ (ppm): -77.3 (3F, s)

[0274] The reaction in Synthesis Example 1 is shown below.

[0275]

[0276] (Synthesis example 2)

[0277] 5.0 g (61 mmol, 1.0 eq.) of 2-methylimidazole, 19.5 g (116 mmol, 1.9 eq.) of trifluoromethanesulfonyl chloride, 12.9 g (122 mmol, 2.0 eq.) of sodium carbonate and 61 mL of acetonitrile as a reaction solvent were added to a 200 mL three-necked flask with a stirrer. The mixture was then stirred at room temperature for 22 hours. The reaction solution was concentrated to a small amount and then concentrated to a flask. 1 As a result of H-NMR analysis, the signal derived from 2-methylimidazole completely disappeared, and a signal derived from 1-trifluoromethanesulfonyl-2-methylimidazole was newly observed.

[0278] The reaction solution was filtered through celite to remove insoluble matter to obtain a filtrate, and acetonitrile was removed from the filtrate to obtain 10.2 g of 1-trifluoromethanesulfonyl-2-methylimidazole.

[0279] [Physical property values]

[0280] 1-Trifluoromethanesulfonyl-2-methylimidazole;

[0281] 1 H-NMR (400MHz, CD3CN) δ (ppm): 7.42 (1H, s), 7.05 (1H, s), 2.56 (3H, s)

[0282] 19 F-NMR (373MHz, CD3CN) δ (ppm): -76.7 (3F, s)

[0283] The reaction of Synthesis Example 2 is shown below.

[0284]

[0285] (Synthesis example 3)

[0286] Take 4-nitroimidazole 5.0g (44mmol), as the reaction solvent of methylene chloride 45mL, add to the capacity of 100mL as the reaction vessel of the three-necked flask equipped with a stirrer. Then drip trifluoromethanesulfonic anhydride 6.3g (22mmol, 0.5eq.), stir at room temperature for 21 hours. The reaction solution is filtered through diatomite and insoluble matter is removed to obtain a filtrate, and methylene chloride is removed from the filtrate to obtain 1-trifluoromethanesulfonyl-4-nitroimidazole 5.2g.

[0287] [Physical property values]

[0288] 1-Trifluoromethanesulfonyl-4-nitroimidazole;

[0289] 1H-NMR (400MHz, CDCl3) δ (ppm): 8.17 (1H, d, J = 1.2Hz), 8.02 (1H, d, J = 1.6Hz)

[0290] 19 F-NMR (373MHz, CDCl3) δ (ppm): -74.6 (3F, s)

[0291] The reaction of Synthesis Example 3 is shown below.

[0292]

[0293] [Example 1]

[0294] 195 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a 20 mL Schlenk tube equipped with a stirrer as a reaction container. Then, a composition containing 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and the quantitative yield was 100%.

[0295] The reaction of Example 1 is shown below.

[0296]

[0297] [Example 2]

[0298] 196 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of dimethylformamide (DMF) as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 228 mg (1.14 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 27 mg (0.20 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and the quantitative yield was 100%.

[0299] The reaction of Example 2 is shown below.

[0300]

[0301] [Example 3]

[0302] 197 mg (1.01 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of dimethyl sulfoxide (DMSO) as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 228 mg (1.14 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and the quantitative yield was 100%.

[0303] The reaction of Example 3 is shown below.

[0304]

[0305] [Example 4]

[0306] 196 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of γ-butyrolactone as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 223 mg (1.12 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 27 mg (0.20 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and the quantitative yield was 100%.

[0307] The reaction of Example 4 is shown below.

[0308]

[0309] [Example 5]

[0310] Take 586 mg (3.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 15 mL of tetrahydrofuran (THF) as a reaction solvent, and add them to a two-necked flask with a capacity of 50 mL and a stirring rod as a reaction container. Then, add a composition containing 720 mg (3.60 mmol, 1.2 eq.) of 1-trifluoromethanesulfonyl imidazole and 67 mg (0.60 mmol, 0.2 eq.) of potassium tert-butoxide to the reaction container, stir at room temperature for 16 hours, and obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and the quantitative yield was 99%.

[0311] The reaction of Example 5 is shown below.

[0312]

[0313] [Example 6]

[0314] 196 mg (1.01 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 222 mg (1.11 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 51 mg (0.52 mmol, 0.5 eq.) of triethylamine was added to the reaction container and stirred at room temperature for 20 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When F-NMR was analyzed, a signal derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and the quantitative yield was 42%, but no side reaction was observed. Specifically, a signal derived from "methyl 2-trifluoromethanesulfonylamino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate" which may be equivalent to a by-product was not confirmed.

[0315] The reaction of Example 6 is shown below.

[0316]

[0317] [Example 7]

[0318] 111 mg (1.02 mmol, 1.0 eq.) of 4-aminophenol as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 222 mg (1.11 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from 4-aminophenyl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 100%.

[0319] The reaction of Example 7 is shown below.

[0320]

[0321] [Example 8]

[0322] 109 mg (1.00 mmol, 1.0 eq.) of 2-aminophenol as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and a stirring bar as a reaction container. Then, a composition containing 202 mg (1.01 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 29 mg (0.21 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 3 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 F-NMR analysis revealed a signal derived from 2-aminophenyl trifluoromethanesulfonate at -75 ppm, with a quantitative yield of 48%, and a signal derived from 1,1,1-trifluoro-N-(2-hydroxyphenyl)methanesulfonamide at -78 ppm, with a quantitative yield of 17%.

[0323] The reaction of Example 8 is shown below.

[0324]

[0325] [Example 9]

[0326] 1.08 g (7.87 mmol, 1.0 eq.) of 4-(2-aminoethyl)phenol as a substrate and 39 mL of tetrahydrofuran as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 1.89 g (9.44 mmol, 1.2 eq.) of 1-trifluoromethanesulfonyl imidazole and 177 mg (1.58 mmol, 0.2 eq.) of potassium tert-butoxide was added to the reaction container and stirred at room temperature for 3 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from 4-(2-aminoethyl)phenyl trifluoromethanesulfonate was confirmed at -75 ppm, and the quantitative yield was 97%.

[0327] The reaction of Example 9 is shown below.

[0328]

[0329] [Example 10]

[0330] 276 mg (2.00 mmol, 1.0 eq.) of 2-(4-hydroxyphenyl)ethanol as a substrate and 10 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 401 mg (2.00 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 14 mg (0.10 mmol, 0.05 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 22 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from 4-(2-hydroxyethyl)phenyl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 92%.

[0331] The reaction of Example 10 is shown below.

[0332]

[0333] [Example 11]

[0334] 139 mg (1.00 mmol, 1.0 eq.) of 2-(4-hydroxyphenyl)ethanol as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 202 mg (1.01 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 20 mg (0.20 mmol, 0.2 eq.) of potassium bicarbonate was added to the reaction container and stirred at room temperature for 30 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from 4-(2-hydroxyethyl)phenyl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 88%.

[0335] The reaction of Example 11 is shown below.

[0336]

[0337] [Example 12]

[0338] 335 mg (2.00 mmol, 1.0 eq.) of L-phenylephrine as a substrate and 10 mL of dimethylformamide as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 400 mg (2.00 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 14 mg (0.10 mmol, 0.05 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 5 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from 3-[(1R)-1-hydroxy-2-(methylamino)ethyl]phenyl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 90%.

[0339] The reaction of Example 12 is shown below.

[0340]

[0341] [Example 13]

[0342] 167 mg (1.00 mmol, 1.0 eq.) of L-phenylephrine as a substrate and 5 mL of dimethylformamide as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 201 mg (1.00 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 20 mg (0.20 mmol, 0.2 eq.) of potassium bicarbonate was added to the reaction container and stirred at room temperature for 22 hours to obtain a reaction solution. Trifluorotoluene was added to the reaction solution as an internal standard. 19 When analyzed by F-NMR, a signal derived from 3-[(1R)-1-hydroxy-2-(methylamino)ethyl]phenyl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 89%.

[0343] The reaction of Example 13 is shown below.

[0344]

[0345] [Example 14]

[0346] 666 mg (5.00 mmol, 1.0 eq.) of 5-hydroxyindole as a substrate and 10 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 1.00 g (5.00 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 138 mg (1.00 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 3 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 F-NMR analysis revealed that a signal derived from indol-5-yl trifluoromethanesulfonate was observed at -74 ppm, with a quantitative yield of 87%. Signals derived from 1-(trifluoromethanesulfonyl)indol-5-yl trifluoromethanesulfonate were observed at -74 ppm and -76 ppm, with a quantitative yield of 5%.

[0347] The reaction of Example 14 is shown below.

[0348]

[0349] [Example 15]

[0350] 134 mg (1.00 mmol, 1.0 eq.) of 6-hydroxyindazole as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 201 mg (1.01 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 27 mg (0.19 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When F-NMR was analyzed, a signal derived from indazol-6-yl trifluoromethanesulfonate was confirmed at -74ppm, and the quantitative yield was 74%. A signal derived from 1-(trifluoromethanesulfonyl)indazol-6-yl trifluoromethanesulfonate was confirmed at -73ppm and -75ppm, and the quantitative yield was 6%. A signal derived from 1-(trifluoromethanesulfonyl)indazol-6-ol was confirmed at -75ppm, and the quantitative yield was 7%.

[0351] The reaction of Example 15 is shown below.

[0352]

[0353] [Example 16]

[0354] 500 mg (2.73 mmol, 1.0 eq.) of 4-hydroxycarbazole as a substrate and 5.4 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 550 mg (2.75 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 75 mg (0.54 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 4 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When analyzed by F-NMR, a signal derived from carbazole-4-yl trifluoromethanesulfonate was confirmed at -72 ppm, and the quantitative yield was 98%.

[0355] The reaction of Example 16 is shown below.

[0356]

[0357] [Example 17]

[0358] 96 mg (1.0 mmol, 1.0 eq.) of 4-hydroxypyridine as a substrate and 5 mL of tetrahydrofuran as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 244 mg (1.22 mmol, 1.2 eq.) of 1-trifluoromethanesulfonyl imidazole and 22 mg (0.20 mmol, 0.2 eq.) of potassium tert-butoxide was added to the reaction container and stirred at 70°C for 5 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When F-NMR was analyzed, a signal derived from pyridin-4-yl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 67%, but no side reaction was observed. Specifically, a signal derived from 1-(trifluoromethanesulfonyl)-4-[(trifluoromethanesulfonyl)oxy]pyridinium, which may be a byproduct, was not confirmed.

[0359] The reaction of Example 17 is shown below.

[0360]

[0361] [Example 18]

[0362] Take 671 mg (5.00 mmol, 1.0 eq.) of pyrrolo[2,3-b]pyridine-5-ol as a substrate and 25 mL of tetrahydrofuran as a reaction solvent, and add them to a two-necked flask with a capacity of 50 mL and a stirring bar as a reaction container. Then, add a composition containing 1.20 g (6.00 mmol, 1.2 eq.) of 1-trifluoromethanesulfonyl imidazole and 112 mg (1.00 mmol, 0.2 eq.) of potassium tert-butoxide to the reaction container, stir at room temperature for 16 hours, and obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When F-NMR was analyzed, a signal derived from pyrrolo[2,3-b]pyridin-5-yl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 91%, but no side reaction was observed. Specifically, a signal derived from 1-(trifluoromethanesulfonyl)-pyrrolo[2,3-b]pyridin-5-yl trifluoromethanesulfonate, which may be a by-product, was not observed.

[0363] The reaction of Example 18 is shown below.

[0364]

[0365] [Example 19]

[0366] Take 169 mg (1.01 mmol, 1.0 eq.) of methyl 2,4-dihydroxybenzoate as a substrate and 5 mL of acetonitrile as a reaction solvent and add them to a Schlenk tube with a capacity of 20 mL and a stirrer as a reaction container. Then add a composition containing 202 mg (1.01 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate to the reaction container and stir at room temperature for 7 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution and 19 F-NMR analysis revealed a signal derived from methyl 2-hydroxy-4-(trifluoromethanesulfonyloxy)benzoate at -74 ppm, with a quantitative yield of 76%. A signal derived from methyl 4-hydroxy-2-[(trifluoromethanesulfonyl)oxy]benzoate was observed at -75 ppm, with a quantitative yield of 5%.

[0367] The reaction of Example 19 is shown below.

[0368]

[0369] [Example 20]

[0370] Take 544 mg (2.00 mmol, 1.0 eq.) of arbutin as a substrate and 10 mL of dimethylformamide as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and a stirring rod as a reaction container. Then, add a composition containing 400 mg (2.00 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 14 mg (0.10 mmol, 0.05 eq.) of potassium carbonate to the reaction container, stir at room temperature for 5 hours, and obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from 4-trifluoromethanesulfonyloxyphenyl β-D-pyranoglucoside was confirmed at -74 ppm, and the quantitative yield was 76%.

[0371] The reaction of Example 20 is shown below.

[0372]

[0373] [Example 21]

[0374] Take 273 mg (1.00 mmol, 1.0 eq.) of arbutin as a substrate and 5 mL of dimethylformamide as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and a stirring rod as a reaction container. Then, add a composition containing 201 mg (1.00 mmol, 1.0 eq.) of 1-trifluoromethanesulfonyl imidazole and 19 mg (0.19 mmol, 0.2 eq.) of potassium bicarbonate to the reaction container, stir at room temperature for 22 hours, and obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from 4-trifluoromethanesulfonyloxyphenyl β-D-pyranoglucoside was confirmed at -74 ppm, and the quantitative yield was 75%.

[0375] The reaction of Example 21 is shown below.

[0376]

[0377] [Example 22]

[0378] 112 mg (1.03 mmol, 1.0 eq.) of 4-aminophenol as a substrate and 5 mL of acetonitrile as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then, a composition containing 238 mg (1.11 mmol, 1.1 eq.) of 2-methyl-1-trifluoromethanesulfonyl imidazole and 27 mg (0.19 mmol, 0.2 eq.) of potassium carbonate was added to the reaction container and stirred at room temperature for 20 hours to obtain a reaction solution. Trifluorotoluene was added as an internal standard to the reaction solution. 19 When F-NMR was analyzed, a signal derived from 4-aminophenyl trifluoromethanesulfonate was confirmed at -74 ppm, and the quantitative yield was 80%, but no side reaction was observed. Specifically, no signal derived from "1,1,1-trifluoro-N-(2-hydroxyphenyl)methanesulfonamide" which may be a byproduct was confirmed.

[0379] The reaction of Example 22 is shown below.

[0380]

[0381] [Example 23]

[0382] (1st reaction)

[0383] Take 196 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then add a composition containing 224 mg (1.12 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate to the reaction container, stir at room temperature for 2 hours to obtain a reaction solution. Add 5 mL of 1 mol / L hydrochloric acid to the reaction solution and adjust to pH = 1, then stir at room temperature for 5 minutes. Add 2.5 mL of 1 mol / L sodium carbonate aqueous solution to the resulting solution and adjust to pH = 7, then transfer to a separatory funnel with 20 mL of tert-butyl methyl ether and 20 mL of tap water to separate the layers. Wash the resulting organic phase with 20 mL of tap water and dry it with sodium sulfate. The obtained solution was filtered and concentrated under reduced pressure to obtain 327 mg of methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoate at an isolated yield of 100%.

[0384] [Physical property values]

[0385] (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoic acid methyl ester;

[0386] 1 H-NMR (400MHz, CDCl3) δ (ppm): 7.30 (2H, d, J = 9.2Hz), 7.22 (2H, d, J = 9.2Hz), 3.74-3 .71 (4H, m), 3.10 (1H, dd, J = 14.0, 5.6Hz), 2.90 (1H, dd, J = 14.0, 8.4Hz), 1.52 (2H, br s).

[0387] 19 F-NMR (373MHz, CDCl3) δ (ppm): -73.2 (3F, s).

[0388] (Reaction 2)

[0389] 327 mg (1.00 mmol, 1.0 eq.) of methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoate obtained in the first reaction, 5 mL of toluene as a reaction solvent, and 0.5 mL of pure water were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. The obtained solution was bubbled with nitrogen for 15 minutes, and 204 mg (1.50 mmol, 1.5 eq.) of 4-methylphenylboric acid, 276 mg (2.00 mmol, 2.0 eq.) of potassium carbonate, and 60 mg (52 μmol, 0.05 eq.) of tetrakis(triphenylphosphine)palladium were taken directly under a nitrogen flow and added to the reaction container. The reaction container was sealed and stirred at 80°C for 6 hours to obtain a reaction solution. 20 mL of ethyl acetate was added to the reaction solution, and the mixture was washed with 20 mL of tap water. The organic phase was then dried with sodium sulfate and concentrated under reduced pressure. 1-Methylcyclohexene was added to the obtained residue as an internal standard, and the residue was concentrated by 1 When analyzed by H-NMR, a signal derived from methyl (2S)-2-amino-3-(4′-methyl[1,1′-biphenyl]-4-yl)propanoate was confirmed, and the quantitative yield was 82%.

[0390] [Physical property values]

[0391] (2S)-2-amino-3-(4'-methyl[1,1'-biphenyl]-4-yl)propanoic acid methyl ester;

[0392] 1 H-NMR (400MHz, CDCl3) δ (ppm): 7.52 (2H, d, J = 8.4Hz), 7.47 (2H, d, J = 8.0Hz), 7.26-7.23 (4H, m), 3.79- 3.74 (4H, m), 3.13 (1H, dd, J = 13.6Hz, 4.8Hz), 2.89 (1H, dd, J = 14.0Hz, 8.4Hz), 2.39 (3H, s), 1.60 (2H, br s).

[0393] The first reaction and the second reaction of Example 23 are shown below.

[0394] First reaction

[0395]

[0396] Second reaction

[0397]

[0398] [Example 24]

[0399] (1st reaction)

[0400] Take 111 mg (1.02 mmol, 1.0 eq.) of 4-aminophenol as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL as a reaction container equipped with a stirrer. Then add a composition containing 222 mg (1.11 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate to the reaction container, stir at room temperature for 2 hours to obtain a reaction solution. Add 5 mL of 1 mol / L hydrochloric acid to the reaction solution and adjust to pH = 1, then stir at room temperature for 5 minutes. Add 2.5 mL of 1 mol / L sodium carbonate aqueous solution to the resulting solution and adjust to pH = 7, then transfer 20 mL of tert-butyl methyl ether and 20 mL of tap water to a separatory funnel for stratification. Wash the resulting organic phase with 20 mL of tap water and dry it with sodium sulfate. The obtained solution was filtered and concentrated under reduced pressure to obtain 241 mg of 4-aminophenyl trifluoromethanesulfonate at an isolated yield of 100%.

[0401] [Physical property values]

[0402] 4-aminophenyl trifluoromethanesulfonate;

[0403] 1 H-NMR (400MHz, CDCl3) δ (ppm): 7.04 (2H, d, J = 8.8Hz), 6.66 (2H, d, J = 9.2Hz), 3.81 (2H, br s).

[0404] 19 F-NMR (373MHz, CDCl3) δ (ppm): -73.2 (3F, s).

[0405] (Reaction 2)

[0406] In a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container, 235 mg (4.04 mmol, 4.0 eq.) of potassium fluoride, 5 mL of tetrahydrofuran as a reaction solvent, and 241 mg (1.00 mmol, 1.0 eq.) of 4-aminophenyl trifluoromethanesulfonate as a substrate were added, and nitrogen was bubbled for 15 minutes. Next, 205 mg (1.51 mmol, 1.5 eq.) of 4-methylphenylboric acid and 39 mg (50 μmol, 0.05 eq.) of bis(tricyclohexylphosphine)palladium diacetate were taken directly under a nitrogen flow and added to the reaction container. The reaction container was sealed and stirred at 60°C for 20 hours to obtain a reaction solution. 20 mL of ethyl acetate was added to the reaction solution, and the mixture was washed with 20 mL of tap water. The organic phase was then dried with sodium sulfate and concentrated under reduced pressure. 1,4-bis(trifluoromethyl)benzene was added to the resulting residue as an internal standard, and the mixture was concentrated under reduced pressure. 1When analyzed by H-NMR, a signal derived from 4-(4-methylphenyl)aniline was confirmed, and the quantitative yield was 99%.

[0407] [Physical property values]

[0408] 4-(4-Methylphenyl)aniline;

[0409] 1 H-NMR (400MHz, CDCl3) δ (ppm): 7.43 (2H, d, J = 8.4Hz), 7.39 (2H, d, J = 8.4Hz), 7.20 (2H, d, J = 8.4Hz), 6.75 (2H, d, J = 8.8Hz), 3.71 (2H, br s), 2.37 (3H, s).

[0410] The first reaction and the second reaction of Example 24 are shown below.

[0411] First reaction

[0412]

[0413] Second reaction

[0414]

[0415] [Example 25]

[0416] (1st reaction)

[0417] Take 196 mg (1.01 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then add a composition containing 223 mg (1.11 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 28 mg (0.20 mmol, 0.2 eq.) of potassium carbonate to the reaction container, stir at room temperature for 2 hours to obtain a reaction solution. Add 5 mL of 1 mol / L hydrochloric acid to the reaction solution and adjust to pH = 1, then stir at room temperature for 5 minutes. Add 2.5 mL of 1 mol / L sodium carbonate aqueous solution to the resulting solution and adjust to pH = 7, then transfer to a separatory funnel with 20 mL of tert-butyl methyl ether and 20 mL of tap water to separate the layers. Wash the resulting organic phase with 20 mL of tap water and dry it with sodium sulfate. The obtained solution was filtered and concentrated under reduced pressure to obtain 328 mg of methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoate at an isolated yield of 100%.

[0418] (Reaction 2)

[0419] Take 328 mg (1.00 mmol, 1.0 eq.) of (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl) propionic acid methyl ester as a substrate, 3 mL of dimethylformamide and 3 mL of triethylamine as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and a stirrer as a reaction container. Nitrogen bubble the resulting solution for 15 minutes, and in this state, tetrakis(triphenylphosphine)palladium 62 mg (54 μmol, 0.05 eq.), copper iodide 15 mg (77 μmol, 0.08 eq.), and 4-ethynyltoluene 179 mg (1.54 mmol, 1.5 eq.) are taken under a nitrogen stream and added to the reaction container. The reaction container is sealed and stirred at 80° C. for 20 hours to obtain a reaction solution. 30 mL of ethyl acetate is added to the reaction solution, and the supernatant is washed with 30 mL, and then the organic phase is dried with sodium sulfate and concentrated under reduced pressure. 1-Methylcyclohexene was added to the obtained residue as an internal standard. 1 When analyzed by H-NMR, a signal derived from methyl (2S)-2-amino-3-{4-[(4-methylphenyl)ethynyl]phenyl}propanoate was confirmed, and the quantitative yield was 91%.

[0420] [Physical property values]

[0421] (2S)-2-amino-3-{4-[(4-methylphenyl)ethynyl]phenyl}propanoic acid methyl ester;

[0422] 1 H-NMR (400MHz, CDCl3) δ (ppm)

[0423] : 7.46 (2H, d, J = 8.4Hz), 7.42 (2H, d, J = 8.0Hz), 7.18-7.14 (4H, m), 3.76-3.72 (4H, m), 3.09 (1H, dd, J = 13.6, 5.6Hz), 2.88 (1H, dd, J = 13.6, 8.0Hz), 2.37 (3H, s), 1.50 (2H, br s).

[0424] The first reaction and the second reaction of Example 25 are shown below.

[0425] First reaction

[0426] Same as Example 23.

[0427] Second reaction

[0428]

[0429] [Example 26]

[0430] (1st reaction)

[0431] Take 196 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then add a composition containing 219 mg (1.09 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 27 mg (0.20 mmol, 0.2 eq.) of potassium carbonate to the reaction container, stir at room temperature for 2 hours to obtain a reaction solution. Add 5 mL of 1 mol / L hydrochloric acid to the reaction solution and adjust to pH = 1, then stir at room temperature for 5 minutes. Add 2.5 mL of 1 mol / L sodium carbonate aqueous solution to the resulting solution and adjust to pH = 7, then transfer to a separatory funnel with 20 mL of tert-butyl methyl ether and 20 mL of tap water to separate the layers. Wash the resulting organic phase with 20 mL of tap water and dry it with sodium sulfate. The obtained solution was filtered and concentrated under reduced pressure to obtain 320 mg of methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoate at an isolated yield of 98%.

[0432] (Reaction 2)

[0433] Take 320 mg (0.98 mmol, 1.0 eq.) of (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl) propionic acid methyl ester as a substrate and 5 mL of dimethylformamide as a reaction solvent and add them to a Schlenk tube with a capacity of 20 mL and a stirrer as a reaction container. Nitrogen bubble the resulting solution for 15 minutes, and in this state, triethylamine 516 mg (5.10 mmol, 5.2 eq.), 4-methylstyrene 239 mg (2.02 mmol, 2.1 eq.), tetrakis(triphenylphosphine)palladium 58 mg (50 μmol, 0.05 eq.) are added to the reaction container under a nitrogen stream. The reaction container is sealed, stirred at 80°C for 16 hours, and then heated to 100°C and stirred for 6 hours to obtain a reaction solution. 30 mL of ethyl acetate is added to the reaction solution, and it is washed with 30 mL of tap water, and then the organic phase is dried with sodium sulfate and concentrated under reduced pressure. 1,4-bis(trifluoromethyl)benzene was added to the obtained residue as an internal standard. 1 Analysis by H-NMR revealed a signal derived from methyl (2S)-2-amino-3-{4-[(E)-2-(4-methylphenyl)vinyl]phenyl}propanoate, and the quantitative yield was 56%.

[0434] [Physical property values]

[0435] (2S)-2-amino-3-{4-[(E)-2-(4-methylphenyl)vinyl]phenyl}propanoic acid methyl ester;

[0436] 1 H-NMR (400MHz, CDCl3) δ (ppm): 7.44 (2H, d, J = 8.4Hz), 7.40 (2H, d, J = 8.0Hz), 7.19-7.16 (4H, m), 7.05-7.04 (2 H, m), 3.76-3.73 (4H, m), 3.09 (1H, dd, J = 13.6, 5.2Hz), 2.87 (1H, dd, J = 14.0, 8.0Hz), 2.36 (3H, s), 1.48 (2H, br s).

[0437] The first reaction and the second reaction of Example 26 are shown below.

[0438] First reaction

[0439] Same as Example 23.

[0440] Second reaction

[0441]

[0442] [Example 27]

[0443] (1st reaction)

[0444] Take 195 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then add a composition containing 221 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonyl imidazole and 27 mg (0.20 mmol, 0.2 eq.) of potassium carbonate to the reaction container, stir at room temperature for 2 hours to obtain a reaction solution. Add 5 mL of 1 mol / L hydrochloric acid to the reaction solution and adjust to pH = 1, then stir at room temperature for 5 minutes. Add 2.5 mL of 1 mol / L sodium carbonate aqueous solution to the resulting solution and adjust to pH = 7, then transfer to a separatory funnel with 20 mL of tert-butyl methyl ether and 20 mL of tap water to separate the layers. Wash the resulting organic phase with 20 mL of tap water and dry it with sodium sulfate. The obtained solution was filtered and concentrated under reduced pressure to obtain 327 mg of methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoate at an isolated yield of 99%.

[0445] (Reaction 2)

[0446] 327 mg (1.00 mmol, 1.0 eq.) of methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate as a substrate and 5 mL of dimethyl sulfoxide as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. The resulting solution was bubbling with nitrogen, and 31 mg (57 μmol, 0.06 eq.) of 1,1'-bis(diphenylphosphino)ferrocene (DPPF) and 11 mg (61 μmol, 0.06 eq.) of palladium (II) chloride were added under a nitrogen flow, and stirred at room temperature for 10 minutes. 383 mg (1.51 mmol, 1.5 eq.) of bis(pinacolato)diboron and 309 mg (3.15 mmol, 3.2 eq.) of potassium acetate were added to the resulting solution, and the container was sealed and stirred at 80°C for 16 hours to obtain a reaction solution. 30 mL of dichloromethane was added to the reaction solution, and the mixture was washed with 30 mL of tap water. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. 1-Methylcyclohexene was added to the residue as an internal standard. 1 When analyzed by H-NMR, a signal derived from methyl (2S)-2-amino-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate was confirmed, and the quantitative yield was 87%.

[0447] [Physical property values]

[0448] (2S)-2-amino-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoic acid methyl ester;

[0449] 1 H-NMR (400MHz, CDCl3) δ (ppm): 7.75 (2H, d, J = 8.0Hz), 7.20 (2H, d, J = 8.0Hz), 3.76-3 .71 (4H, m), 3.11 (1H, dd, J = 13.6, 5.6Hz), 2.88 (1H, dd, J = 13.2, 8.0Hz), 1.73 (2H, br s), 1.34(12H, s).

[0450] The first reaction and the second reaction of Example 27 are shown below.

[0451] First reaction

[0452] Same as Example 23.

[0453] Second reaction

[0454]

[0455] [Reference Example 1]

[0456] Take 695 mg (5.03 mmol, 1.0 eq.) of 2-(4-hydroxyphenyl)ethanol as a substrate and 25 mL of dichloromethane as a reaction solvent and add them to a 30 mL two-necked eggplant flask equipped with a stirrer. Then add 521 mg (5.15 mmol, 1.0 eq.) of triethylamine to the reaction container and stir while cooling the reaction container with ice. Add 1.44 g (5.10 mmol, 1.0 eq.) of trifluoromethanesulfonic anhydride dropwise, then return the reaction container to room temperature and stir for 2 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution and stir by 19 When F-NMR was analyzed, a signal derived from 4-(2-hydroxyethyl)phenyl trifluoromethanesulfonate was confirmed at -74ppm, and the quantitative yield was 40%. In addition, as a by-product, a signal derived from 4-[2-(trifluoromethanesulfonyloxy)ethyl]phenyl trifluoromethanesulfonate was observed at -73ppm and -75ppm, and the quantitative yield was 29%.

[0457] The reaction of Reference Example 1 is shown below.

[0458]

[0459] [Reference Example 2]

[0460] 196 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 10 mL of dimethylformamide as a reaction solvent were added to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. Then 273 mg (1.00 mmol, 1.0 eq.) of 4-nitrophenyl trifluoromethanesulfonate and 278 mg (2.01 mmol, 2.0 eq.) of potassium carbonate were added to the reaction container and stirred at room temperature for 2 hours to obtain a reaction solution. Trifluorotoluene was added to the reaction solution as an internal standard. 19 When F-NMR analysis was performed, a signal derived from methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was confirmed at -74 ppm, and a signal derived from methyl (2S)-2-(4-nitroanilino)-3-[4-(trifluoromethanesulfonyloxy)phenyl]propionate was confirmed at -74 ppm, and the quantitative yields were 40% and 27%, respectively.

[0461] The reaction of Reference Example 2 is shown below.

[0462]

[0463] [Reference Example 3]

[0464] Take 195 mg (1.00 mmol, 1.0 eq.) of L-tyrosine methyl ester as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a 20 mL Schlenk tube with a stirrer as a reaction container. Add 106 g (1.05 mmol, 1.0 eq.) of triethylamine to the reaction container, and stir while cooling the reaction container to -20°C. Add 105 μL (1.00 mmol, 1.0 eq.) of trifluoromethanesulfonyl chloride dropwise to the reaction container, and stir at -20°C for 2 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 F-NMR analysis revealed that a signal derived from methyl (2S)-2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propionate was observed at -74 ppm, and the quantitative yield was 32%. In addition, two signals derived from by-products were observed at -74 ppm, and the quantitative yields were 10% and 8%, respectively.

[0465] The reaction of Reference Example 3 is shown below.

[0466]

[0467] [Reference Example 4]

[0468] Take 134 mg (1.00 mmol, 1.0 eq.) of 5-hydroxyindole as a substrate and 4 mL of dichloromethane as a reaction solvent, and add them to a 20 mL Schlenk tube with a stirrer as a reaction container. Add 120 mg (1.19 mmol, 1.2 eq) of triethylamine to the reaction container, and stir while cooling the reaction container to -20°C. Dissolve 105 μL (1.00 mmol, 1.0 eq.) of trifluoromethanesulfonyl chloride in 1 mL of dichloromethane, and add it dropwise to the reaction container. Cool the reaction container to -20°C, and stir for 1 hour in this state to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 F-NMR analysis revealed a signal derived from indol-5-yl trifluoromethanesulfonate at -74 ppm, with a quantitative yield of 22%. In addition, a signal derived from a by-product was observed at -73 ppm, with a quantitative yield of 29%.

[0469] The reaction of Reference Example 4 is shown below.

[0470]

[0471] [Reference Example 5]

[0472] Take 13.8g (99.9mmol, 1.4eq.) of 2-(4-hydroxyphenyl)ethanol as a substrate and add it to a 300ml SUS autoclave with a stirrer as a reaction vessel, then seal the reaction vessel and decompress it with a vacuum pump. Take 10.1g (100mmol, 1.4eq.) of triethylamine and 200mL of acetonitrile as a reaction solvent and transfer them to the reaction vessel with a cannula. Cool the reaction vessel with dry ice and fill it with 10.6g (69.4mmol, 1.0eq.) of trifluoromethanesulfonyl fluoride from a gas tank. Return the reaction vessel to room temperature and stir for 18 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution and 19 F-NMR analysis revealed a signal derived from 4-(2-hydroxyethyl)phenyl trifluoromethanesulfonate at -74 ppm, with a quantitative yield of 33%. In addition, two signals derived from by-products were observed at -74 ppm, with yields of 15% and 11%, respectively.

[0473] The reaction of Reference Example 5 is shown below.

[0474]

[0475] In the examples of the first aspect, the formation of by-products can be suppressed, and a trifluoromethanesulfonated compound can be obtained at a good yield. The phenolic hydroxyl group can be selectively trifluoromethanesulfonated.

[0476] (Synthesis Example 4)

[0477] [First reaction]

[0478] 5.0 g (61 mmol, 1.0 eq. = molar equivalent ratio, the same below), 19.5 g (116 mmol, 1.9 eq.) of 2-methylimidazole, 12.9 g (122 mmol, 2.0 eq.) of sodium carbonate and 61 mL of acetonitrile as a reaction solvent were added to a 200 mL three-necked flask with a stirrer. The mixture was then stirred at room temperature (about 25°C, the same below) for 22 hours to obtain a first reaction solution. The reaction solution was concentrated to a small amount and then stirred at room temperature (about 25°C, the same below) for 22 hours. 1 As a result of H-NMR analysis, the signal derived from 2-methylimidazole completely disappeared, and a signal derived from trifluoromethanesulfonyl-2-methylimidazole was newly observed, thereby confirming that the first reaction had been completed.

[0479] The first reaction liquid was filtered through diatomaceous earth (Celite, registered trademark = diatomaceous earth calcined with sodium carbonate, the same below) to remove sodium carbonate to obtain a filtrate, and acetonitrile was removed from the filtrate to obtain 10.2 g of trifluoromethanesulfonyl-2-methylimidazole (also referred to as "1-trifluoromethanesulfonyl-2-methylimidazole").

[0480] [Physical property values]

[0481] Trifluoromethanesulfonyl-2-methylimidazole;

[0482] 1 H-NMR (400MHz, CD3CN) δ (ppm): 7.42 (1H, s), 7.05 (1H, s), 2.56 (3H, s)

[0483] 19 F-NMR (373MHz, CD3CN) δ (ppm): -76.7 (3F, s)

[0484] [Second reaction]

[0485] 122 mL of dichloromethane and 10.0 g (61 mmol, 1.2 eq.) of methyl trifluoromethanesulfonate were added to 10.2 g of trifluoromethanesulfonyl-2-methylimidazole obtained in the first reaction. Then, the mixture was stirred at room temperature for 22 hours to obtain a second reaction solution. The reaction solution was concentrated to a small amount and then precipitated by 1 H-NMR analysis revealed that the signal derived from trifluoromethanesulfonyl-2-methylimidazole completely disappeared, and a signal derived from trifluoromethanesulfonyl imidazolium, i.e., trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate, which was the target product of the second reaction, was observed, thereby confirming that the second reaction had been completed.

[0486] The second reaction solution was concentrated, and 100 ml of tert-butyl methyl ether was added. The mixture was then stirred at room temperature for 22 hours. The precipitated crystals were filtered to obtain crystals, which were dried under reduced pressure to obtain 16.7 g of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate at a yield of 72%.

[0487] [Physical property values]

[0488] Trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate;

[0489] 1 H-NMR (400MHz, CD3CN) δ (ppm): 7.83 (1H, d, J = 2.8Hz), 7.61 (1H, d, J = 2.4Hz), 3.85 (3H, s), 2.84 (3H, s)

[0490] 19 F-NMR (373MHz, CD3CN) δ (ppm): -74.1 (3F, s), -79.3 (3F, s)

[0491] The first reaction and the second reaction of Synthesis Example 4 are shown below.

[0492]

[0493] (Synthesis Example 5)

[0494] [First reaction]

[0495] 5.0 g (72 mmol, 1.0 eq.) of 1,2,4-triazole, 23.0 g (137 mmol, 1.9 eq.) of trifluoromethanesulfonyl chloride, 15.3 g (144 mmol, 2.0 eq.) of sodium carbonate and 72 mL of acetonitrile were added to a 200 mL three-necked flask with a stirrer. The mixture was stirred at room temperature for 3 days to obtain the first reaction solution. The reaction solution was concentrated to a small amount and then 1 As a result of H-NMR analysis, the signal derived from 1,2,4-triazole completely disappeared, and a signal derived from trifluoromethanesulfonyl-1,2,4-triazole was newly observed, thereby confirming that the first reaction had been completed.

[0496] The first reaction liquid was filtered through celite, and acetonitrile was removed from the obtained filtrate to obtain 12.1 g of trifluoromethanesulfonyl-1,2,4-triazole.

[0497] [Physical property values]

[0498] Trifluoromethanesulfonyl-1,2,4-triazole;

[0499] 1 H-NMR (400MHz, CD3CN) δ (ppm): 9.05 (1H, s), 8.38 (1H, s)

[0500] 19 F-NMR (373MHz, CD3CN) δ (ppm): -75.2 (3F, s)

[0501] [Second reaction]

[0502] 144 mL of dichloromethane and 11.8 g (72 mmol, 1.2 eq.) of methyl trifluoromethanesulfonate were added to 12.1 g of trifluoromethanesulfonyl-1,2,4-triazole obtained in the first reaction. Then, the mixture was stirred at room temperature for 22 hours to obtain a second reaction solution. The reaction solution was concentrated to a small amount and then precipitated by 1 H-NMR analysis revealed that the signal derived from trifluoromethanesulfonyl-1,2,4-triazole completely disappeared, and a signal derived from trifluoromethanesulfonyl-4-methyl-1,2,4-triazolium trifluoromethanesulfonate, the target product of the second reaction, was observed, thereby confirming that the second reaction had been completed.

[0503] The second reaction solution was concentrated, and 100 ml of tert-butyl methyl ether was added. The mixture was then stirred at room temperature for 22 hours. The precipitated crystals were filtered to obtain crystals, which were dried under reduced pressure to obtain 16.5 g of trifluoromethanesulfonyl-4-methyl-1,2,4-triazolium trifluoromethanesulfonate at a yield of 63%.

[0504] [Physical property values]

[0505] Trifluoromethanesulfonyl-4-methyl-1,2,4-triazolium trifluoromethanesulfonate;

[0506] 1 H-NMR (400MHz, CD3CN) δ (ppm): 10.40 (1H, s), 9.00 (1H, s), 4.07 (3H, s)

[0507] 19 F-NMR (373MHz, CD3CN) δ (ppm): -71.5 (3F, s), -79.3 (3F, s)

[0508] The first reaction and the second reaction of Synthesis Example 5 are shown below.

[0509]

[0510] (Synthesis Example 6)

[0511] [First reaction]

[0512] Take 5.0g (73mmol, 1.0eq.) of imidazole, 23.5g (139mmol, 1.9eq.) of trifluoromethanesulfonyl chloride, 15.6g (122mmol, 2.0eq.) of sodium carbonate and 73mL of acetonitrile as a reaction solvent and add them into a 200mL three-necked flask with a stirrer. Then, stir at room temperature for 16 hours to obtain the first reaction solution. The reaction solution is concentrated to a small amount and then 1 As a result of H-NMR analysis, the signal derived from imidazole completely disappeared, and a signal derived from trifluoromethanesulfonyl imidazole was newly observed, thereby confirming that the first reaction had been completed.

[0513] The first reaction liquid was filtered through celite to remove sodium carbonate to obtain a filtrate, and acetonitrile was removed from the filtrate to obtain 9.7 g of trifluoromethanesulfonyl imidazole (also referred to as "1-trifluoromethanesulfonyl imidazole").

[0514] [Physical property values]

[0515] Trifluoromethanesulfonyl imidazole;

[0516] 1H-NMR (400MHz, CD3CN) δ (ppm): 8.15 (1H, s), 7.56 (1H, s), 7.29 (1H, s)

[0517] 19 F-NMR (373MHz, CD3CN) δ (ppm): -77.3 (3F, s)

[0518] [Second reaction]

[0519] 50 mL of dichloromethane and 7.9 g (48 mmol, 1.0 eq.) of methyl trifluoromethanesulfonate were added to 9.7 g of trifluoromethanesulfonyl imidazole obtained in the first reaction. Then, the mixture was stirred at room temperature for 14 hours to obtain a second reaction solution. The reaction solution was concentrated to a small amount and then precipitated by 1 H-NMR analysis revealed that the signal derived from trifluoromethanesulfonyl imidazole completely disappeared, and a signal derived from trifluoromethanesulfonyl imidazolium, i.e., trifluoromethanesulfonyl-3-methylimidazolium trifluoromethanesulfonate, which was the target product of the second reaction, was observed, thereby confirming that the second reaction had been completed.

[0520] The second reaction solution was concentrated, and 100 ml of tert-butyl methyl ether was added. The mixture was then stirred at room temperature for 15 hours. The precipitated crystals were filtered to obtain crystals, which were dried under reduced pressure to obtain 13.6 g of trifluoromethanesulfonyl-3-methylimidazolium trifluoromethanesulfonate at a yield of 50%.

[0521] [Physical property values]

[0522] Trifluoromethanesulfonyl-3-methylimidazolium trifluoromethanesulfonate;

[0523] 1 H-NMR (400MHz, CD3CN) δ (ppm): 9.45 (1H, s), 7.97 (1H, m), 7.74 (1H, m), 4.01 (3H, s)

[0524] 19 F-NMR (373MHz, CD3CN) δ (ppm): -73.9 (3F, s), -79.3 (3F, s)

[0525] The first reaction and the second reaction of Synthesis Example 6 are shown below.

[0526]

[0527] (Synthesis Example 7)

[0528] 0.81 g (3.8 mmol, 1.0 eq.) of trifluoromethanesulfonyl-2-methylimidazole obtained in the same manner as in the first reaction of Synthesis Example 4 and 4 mL of dichloromethane were added to a 20 mL Schlenk tube equipped with a stirrer as a reaction vessel. 0.68 g (3.8 mmol, 1.0 eq.) of ethyl trifluoromethanesulfonate was added, followed by stirring at 60° C. for 2 hours. The reaction solution was concentrated to a small amount and then 1 H-NMR analysis revealed that the signal derived from trifluoromethanesulfonyl-2-methylimidazole completely disappeared, and the signal derived from the target product, trifluoromethanesulfonyl imidazolium, i.e., trifluoromethanesulfonyl-3-ethyl-2-methylimidazolium trifluoromethanesulfonate, was observed, thereby confirming that the second reaction had been completed.

[0529] 20 mL of tert-butyl methyl ether was added to the reaction solution, followed by stirring at room temperature for 1 hour. The precipitated crystals were filtered off by suction and dried under reduced pressure to obtain 1.3 g of trifluoromethanesulfonyl-3-ethyl-2-methylimidazolium trifluoromethanesulfonate at a yield of 88%.

[0530] [Physical property values]

[0531] Trifluoromethanesulfonyl-3-ethyl-2-methylimidazolium trifluoromethanesulfonate;

[0532] 1 H-NMR (400MHz, CD3CN) δ (ppm): 7.86 (1H, d, J = 2.8Hz), 7.69 (1H, d, J = 2.4Hz), 4.25 (2H, q, J = 7.6Hz), 2.86 (3H, s), 1.47 (3H, t, J = 7.6Hz)

[0533] 19 F-NMR (373MHz, CD3CN) δ (ppm): -74.1 (3F, s), -79.3 (3F, s)

[0534] The reaction of Synthesis Example 7 is shown below.

[0535]

[0536] [Example 28]

[0537] Take 93 mg (1.0 mmol, 1.0 eq.) of aniline as a substrate and 5 mL of acetonitrile as a reaction solvent, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. While cooling the Schlenk tube in an ice bath, further add a composition containing two components, 0.95 g (2.5 mmol, 2.5 eq.) of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate and 51 mg (0.5 mmol, 0.5 eq.) of triethylamine to the Schlenk tube. After removing the aforementioned ice bath, stir at room temperature for 2 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from N-phenyltrifluoromethanesulfonimide was confirmed at -71 ppm, and the quantitative yield was 98%.

[0538] The reaction of Example 28 is shown below.

[0539]

[0540] [Example 29]

[0541] Take 73 mg (1.0 mmol, 1.0 eq.) of butylamine as a substrate and 5 mL of acetonitrile, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. While cooling the Schlenk tube in an ice bath, further add a composition containing two components, 0.95 g (2.5 mmol, 2.5 eq.) of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate and 51 mg (0.5 mmol, 0.5 eq.) of triethylamine to the Schlenk tube. After removing the aforementioned ice bath, stir at room temperature for 24 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 F-NMR analysis revealed a signal derived from N-butyl trifluoromethanesulfonimide at -73 ppm and a signal derived from N-butyl trifluoromethanesulfonamide at -78 ppm. The quantitative yields were 94% for N-butyl trifluoromethanesulfonimide and 5% for N-butyl trifluoromethanesulfonamide.

[0542] The reaction of Example 29 is shown below.

[0543]

[0544] [Example 30]

[0545] Take 0.12 g (1.0 mmol, 1.0 eq.) of 1-phenylethylamine as a substrate and 5 mL of acetonitrile, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. While cooling the Schlenk tube in an ice bath, further add a composition containing two components, 0.95 g (2.5 mmol, 2.5 eq.) of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate and 51 mg (0.5 mmol, 0.5 eq.) of triethylamine to the Schlenk tube. After removing the aforementioned ice bath, stir at room temperature for 2 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, through 19 When analyzed by F-NMR, a signal derived from N-(1-phenylethyl)trifluoromethanesulfonamide was confirmed at -79 ppm, and the quantitative yield was 100%.

[0546] The reaction of Example 30 is shown below.

[0547]

[0548] [Example 31]

[0549] Take 0.15 g (1.0 mmol, 1.0 eq.) of 6-isopropyl-3-methylphenol as a substrate and 5 mL of acetonitrile, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. While cooling the Schlenk tube in an ice bath, further add a composition containing two components, 0.57 g (1.5 mmol, 1.5 eq.) of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate and 51 mg (0.5 mmol, 0.5 eq.) of triethylamine to the Schlenk tube. After removing the aforementioned ice bath, stir at room temperature for 2 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, through 19 When analyzed by F-NMR, a signal derived from 2-isopropyl-5-methylphenyl trifluoromethanesulfonate was confirmed at -75 ppm, and the quantitative yield was 99%.

[0550] The reaction of Example 31 is shown below.

[0551]

[0552] [Example 32]

[0553] Take 0.31 g (3.0 mmol, 1.0 eq.) of methyl lactate as a matrix and 15 mL of acetonitrile, and add them to a 30 mL two-necked flask equipped with a stirrer. While cooling the two-necked flask in an ice bath, further add a composition containing two components, 1.70 g (4.5 mmol, 1.5 eq.) of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate and 91 mg (0.9 mmol, 0.3 eq.) of triethylamine into the two-necked flask. After removing the aforementioned ice bath, stir at room temperature for 3 hours to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from methyl 2-trifluoromethanesulfonyloxypropionate was confirmed at -76 ppm, and the quantitative yield was 71%.

[0554] The reaction of Example 32 is shown below.

[0555]

[0556] [Example 33]

[0557] Take 0.33g (2.5mmol, 1.0eq.) of ethyl acetoacetate as a substrate, 12.5mL of tetrahydrofuran as a reaction solvent, and 0.10g (2.5mmol, 1.0eq.) of sodium hydride (60% by mass oil dispersion), add them to a 30mL two-necked flask equipped with a stirrer, and then stir at room temperature for 10 minutes. Next, add 1.13g (3.0mmol, 1.2eq.) of trifluoromethanesulfonyl-2,3-dimethylimidazolium trifluoromethanesulfonate to the two-necked flask, and stir at room temperature for 1 hour to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from ethyl (Z)-3-trifluoromethanesulfonyloxy-2-butenoate was confirmed at -76 ppm, and the quantitative yield was 87%.

[0558] The reaction of Example 33 is shown below.

[0559]

[0560] [Example 34]

[0561] Take 93 mg (1.0 mmol, 1.0 eq.) of aniline as a substrate and 5 mL of acetonitrile, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. While cooling the Schlenk tube in an ice bath, further add a composition containing two components, 0.91 g (2.5 mmol, 2.5 eq.) of trifluoromethanesulfonyl-3-methylimidazolium trifluoromethanesulfonate and 51 mg (0.5 mmol, 0.5 eq.) of triethylamine into the Schlenk tube. Remove the aforementioned ice bath, stir at room temperature for 1 hour, and obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from N-phenyltrifluoromethanesulfonimide was confirmed at -71 ppm, and the quantitative yield was 93%.

[0562] The reaction of Example 34 is shown below.

[0563]

[0564] [Example 35]

[0565] Take 47 mg (0.5 mmol, 1.0 eq.) of aniline as a substrate and 2.5 mL of acetonitrile, and add them to a Schlenk tube with a capacity of 20 mL and equipped with a stirrer as a reaction container. While cooling the Schlenk tube in an ice bath, further add a composition containing two components, 0.49 g (1.3 mmol, 2.5 eq.) of trifluoromethanesulfonyl-3-ethyl-2-methylimidazolium trifluoromethanesulfonate synthesized by the method described in Example 4 and 25 mg (0.25 mmol, 0.5 eq.) of triethylamine into the Schlenk tube. Remove the aforementioned ice bath, and then stir at room temperature for 1 hour to obtain a reaction solution. Add trifluorotoluene as an internal standard to the reaction solution, and 19 When analyzed by F-NMR, a signal derived from N-phenyltrifluoromethanesulfonimide was confirmed at -71 ppm, and the quantitative yield was 92%.

[0566] The reaction of Example 35 is shown below.

[0567]

[0568] As described above, the trifluoromethanesulfonyl imidazolium salts or triazolium salts obtained in Synthesis Examples 4 to 7 were used for trifluoromethanesulfonylation, and thus they exhibited excellent performance as trifluoromethanesulfonylating agents for various substrates.

[0569] Industrial Applicability

[0570] The triflation agent composition of the present disclosure can be used as a triflation agent composition under industrially feasible conditions in the synthesis of a raw material or an intermediate of a pharmaceutical.

[0571] While the present disclosure has been described in detail and with reference to specific embodiments, it will be apparent to one skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the present invention.

[0572] This application is based on the Japanese patent application (Japanese Patent Application No. 2022-076302) filed on May 2, 2022, the contents of which are incorporated herein by reference.

Claims

1. A trifluoromethanesulfonylating agent composition comprising a compound represented by the following general formula (1) or (11), In the general formulas (1) and (11), R 1 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms, R 2 is a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms, X is a nitrogen atom or C(R 3 ), Y is a nitrogen atom or C(R 4 ), R 3 is a hydrogen atom, a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms, R 4 is a hydrogen atom, a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 6 to 14 carbon atoms, R 2 With R 3 optionally bonded to form a ring, R 2 With R 4 optionally bonded to form a ring, n is an integer from 1 to 3, There are multiple R 2 In the case of R 2 Optionally the same or different, there are multiple R 3 In the case of R 3 Optional: the same or different, In the general formula (11), R 5 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms, Z - It is an anion.

2. The trifluoromethanesulfonylating agent composition according to claim 1, comprising: The compound represented by the general formula (1), and Any base selected from the group consisting of aliphatic organic bases, heterocyclic group-containing organic bases and inorganic bases.

3. The trifluoromethanesulfonylating agent composition according to claim 2, in, In the general formula (1), X is C(R 3 ), R 1 , R 2 and R 3 are each independently a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or an isopropyl group.

4. The trifluoromethanesulfonylating agent composition according to claim 2, in, The organic base is selected from the group consisting of secondary amines, tertiary amines, alkoxides, and organic bases containing a heterocyclic group having a nitrogen atom and having 4 or more carbon atoms.

5. The trifluoromethanesulfonylating agent composition according to claim 2, in, The inorganic base is selected from the group consisting of potassium salts and sodium salts.

6. The trifluoromethanesulfonylating agent composition according to claim 2, in, The base is any one selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, lithium methoxide, lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, triethylamine, tri-n-propylamine, tributylamine, diisopropylethylamine, N,N-diethylcyclohexylamine, 1,8-diazabicyclo[5.4.0]undecene, and 1,5-diazabicyclo[4.3.0]nonene.

7. A method for producing a trifluoromethanesulfonyloxy compound, in, The trifluoromethanesulfonylating agent composition according to any one of claims 2 to 6 is reacted with an aromatic hydroxy compound represented by the general formula (2), Ar-OH(2) In the general formula (2), Ar represents an aromatic ring group or a substituted aromatic ring group.

8. The method for producing a trifluoromethanesulfonyloxy compound according to claim 7, in, In the general formula (2), Ar represents an aromatic ring group, and the aromatic ring group is an aromatic heterocyclic group.

9. The method for producing a trifluoromethanesulfonyloxy compound according to claim 7, in, In the general formula (2), Ar represents a substituted aromatic ring group, and the substituent of the substituted aromatic ring group is a lower alkyl group, a lower alkoxycarbonyl group, a lower alkyl group, a β-D-pyranoglucopyranoside group, an amino group, a lower alkylamino group or a hydroxyl group.

10. The method for producing a trifluoromethanesulfonyloxy compound according to claim 7, in, The reaction is carried out at a reaction temperature of 150°C or less.

11. The method for producing a trifluoromethanesulfonyloxy compound according to claim 7, in, The reaction solution after the reaction is post-treated with an acidic aqueous solution.

12. The trifluoromethanesulfonylating agent composition according to claim 1, in, The compound represented by the general formula (11) is a compound represented by the following general formula (11a), In the general formula (11a), R 11 , R 12 and R 15 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms, Xa is a nitrogen atom or C(R 13 ), R 13 is a hydrogen atom, a linear alkyl group having 1 to 6 carbon atoms, or a branched alkyl group having 3 to 6 carbon atoms, R 12 With R 13 optionally bonded to form a ring, Z - It is an anion.

13. The trifluoromethanesulfonylating agent composition according to claim 12, in, Z in the general formula (11a) - is a trifluoromethanesulfonate anion, a fluoromethanesulfonate anion, a methanesulfonate anion or a sulfonate anion.

14. The trifluoromethanesulfonylating agent composition according to claim 12, in, Xa in the general formula (11a) is C(R 13 ).

15. The trifluoromethanesulfonylating agent composition according to claim 12, in, Xa in the general formula (11a) is C(R 13 ), R 11 , R 12 , R 13 and R 15 are each independently a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or an isopropyl group.

16. A method for producing a trifluoromethanesulfonyl compound, in, The triflation agent composition according to any one of claims 12 to 15 is reacted with at least one substrate selected from the group consisting of a compound having a phenolic hydroxyl group, a compound having an alcoholic hydroxyl group, a ketone, a primary amine and a secondary amine.

Images