Trifluoromethanesulfonating agent composition and method for producing trifluoromethanesulfonyloxy compound

Abstract

The present disclosure provides: a trifluoromethanesulfonating agent composition which contains a specific base and a compound that is represented by general formula (1) set forth in the description; and a method for producing a trifluoromethanesulfonyloxy compound by reacting the trifluoromethanesulfonating agent composition with a compound that is represented by general formula (2) set forth in the description.

Description

Trifluoromethanesulfonylating agent composition and method for producing trifluoromethanesulfonyloxy compound

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

[0002] In the synthesis of pharmaceutical active ingredients or intermediates, trifluoromethanesulfonylation of substrates having various functional groups is carried out. Trifluoromethanesulfonylation of phenolic hydroxyl groups is an important reaction in the synthesis of pharmaceutical active ingredients or intermediates. Examples of such reactions 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-phenyltriflimide (Patent Document 4), a method of reacting a substrate having a phenolic hydroxyl group with 5-chloro-2-pyridyltriflimide (Patent Document 5), a method of reacting a substrate having a phenolic hydroxyl group with 4-nitrophenyltrifluoromethanesulfonate (Non-Patent Document 3), and a method of reacting a substrate having a phenolic hydroxyl group with 2-pyridyltriflimide (Patent Document 6).

[0003] In addition to substrates having a phenolic hydroxyl group, trifluoromethanesulfonylation of ketones, primary amines, or secondary amines has also been carried out. As a trifluoromethanesulfonylation reaction, for example, Non-Patent Documents 4 and 5 describe a method of reacting a metalloenolate, a substrate having a phenolic hydroxyl group, or a secondary amine with N-phenyltriflimide. Furthermore, Non-Patent Document 6 describes a method of reacting a metalloenolate with N-2-pyridyltriflimide, or a metalloenolate with N-5-chloro-2-pyridyltriflimide. Non-Patent Documents 7 and 8 describe a method of reacting a ketone with trifluoromethanesulfonic anhydride.

[0004] Chinese Patent Application Publication No. 104230960, Japanese Patent Application Publication No. 2002-128752, International Publication No. 2011 / 095625, International Publication No. 2014 / 190271, International Publication No. 2013 / 044092, International Publication No. 2007 / 073503

[0005] P. Kancharla. et al, Journal of Medical Chemistry, 2020, 63, 6179-6202. D. Xi. et al, European Journal of Medicinal Chemistry. 2019, 178, 802-817. M. Lesperance. et al., Steroids. 2018, 140, 104-113J. B; Hendrickson. et al., Tetrahedron Letters, 1973, 46, 4607-4610. J. E. McMurry. et al, Tetrahedron Letters, 1983, 10, 979-982. d. L. Comins. et al, Tetrahedron Letters, 1992, 42, 6299-6302. M. Tranchant. et al, Tetrahedron, 2002, 58, 8425-8432. P. J. Stang. et al., Synthesis. 1980, 4, 283-284.

[0006] However, there is still room for further study of trifluoromethanesulfonylation reagents from the viewpoints of economy and reduction of by-products.

[0007] The present disclosure has been made in view of the above circumstances. An object of the present disclosure is to provide a trifluoromethanesulfonylating agent composition capable of trifluoromethanesulfonylation of a substrate having a functional group such as a phenolic hydroxyl group. Another object of the present disclosure is to provide an efficient and industrially feasible method for producing a trifluoromethanesulfonyloxy compound.

[0008] In view of the above problems, the present inventors have conducted extensive research. As a result, they have found that a trifluoromethanesulfonylating agent composition containing a specific trifluoromethanesulfonylating agent according to the present disclosure can trifluoromethanesulfonylate a substrate having a functional group such as a phenolic hydroxyl group while suppressing the production of by-products. They have also found that a trifluoromethanesulfonyloxy compound can be isolated from the reaction solution after the trifluoromethanesulfonylation reaction by simply performing a general post-treatment procedure, thereby efficiently obtaining the trifluoromethanesulfonyloxy compound. Furthermore, they have found that the trifluoromethanesulfonylating agent composition containing a specific base can be used to achieve excellent yields with good reproducibility.

[0009] That is, the present disclosure provides the inventions described in the following [1] to

[10] .

[0010] [1] A trifluoromethanesulfonylating agent composition comprising a compound represented by the following general formula (1) and a non-nucleophilic strong base: (In general formula (1), R １ is a hydrogen atom, a halogen atom, or an aliphatic hydrocarbon group having 1 to 6 carbon atoms; R ２ is a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms, and X is a nitrogen atom or C(R ３ ), and Y is a nitrogen atom or C(R ４ ) and R ３is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; ４ is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; ２ and R ３ may be bonded to form a ring, and R ２ and R ４ may be bonded to form a ring, and n is an integer of 1 to 3. ２ R when there are multiple ２ may be the same or different, R ３ R when there are multiple ３ may be the same or different.)

[0011] [2] The trifluoromethanesulfonylating agent composition according to [1], wherein the non-nucleophilic strong base is a compound represented by the following general formula (A): (In general formula (A), R １００ ~R １０２ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; R １０３ represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 3 to 14 carbon atoms, or NR １０４ R １０５ and R １０４ , R １０５ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; R １００ and R １０１ may be bonded to form a ring, and R １０２ and R １０３ may be bonded to form a ring.)

[0012] [3] In the general formula (1), X is C(R ３ ) and R １ , R ２ , and R ３are each independently a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

[0013] [4] The trifluoromethanesulfonylating agent composition according to any one of [1] to [3], wherein the non-nucleophilic strong base is a compound having a nitrogen atom and a heterocyclic group having 4 or more carbon atoms.

[0014] [5] The trifluoromethanesulfonylating agent composition according to any one of [1] to [4], wherein the non-nucleophilic strong base is 1,8-diazabicyclo[5.4.0]undecene, 1,5-diazabicyclo[4.3.0]nonene, or 1,1,3,3-tetramethylguanidine.

[0015] [6] The trifluoromethanesulfonylating agent composition according to any one of [1] to [5], (wherein Ar represents an aromatic ring group or a substituted aromatic ring group) with an aromatic hydroxyl compound represented by the following general formula (2):

[0016] [7] The method for producing a trifluoromethanesulfonyloxy compound according to [6], wherein, in the general formula (2), Ar represents an aromatic ring group, and the aromatic ring group is an aromatic heterocyclic group.

[0017] [8] The method for producing a trifluoromethanesulfonyloxy compound according to [6], wherein, in the general formula (2), Ar represents a substituted aromatic ring group, and the substituted aromatic ring group has a substituent that is a lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a β-D-glucopyranoside group, an amino group, a lower alkylamino group, or a hydroxyl group.

[0018] [9] The method for producing a trifluoromethanesulfonyloxy compound according to any one of [6] to [8], wherein the reaction is carried out at a reaction temperature of 150° C. or lower.

[0019]

[10] The method for producing a trifluoromethanesulfonyloxy compound according to any one of [6] to [9], wherein the reaction solution after completion of the reaction is post-treated with an acidic aqueous solution.

[0020] According to the present disclosure, it is possible to provide a trifluoromethanesulfonylating agent composition capable of trifluoromethanesulfonylation of a substrate having a functional group such as a phenolic hydroxyl group. It is also possible to provide an industrially feasible and efficient method for producing a trifluoromethanesulfonyloxy compound using the trifluoromethanesulfonylating agent composition. Furthermore, since the trifluoromethanesulfonylating agent composition contains a specific base, it is possible to provide a method for producing a trifluoromethanesulfonyloxy compound with good reproducibility and excellent yield.

[0021] The present disclosure provides a method for producing a trifluoromethanesulfonyloxy compound with good reproducibility and excellent yield, and the reason for this is presumed to be as follows: Inorganic bases such as potassium carbonate have low solubility in reaction solvents and may contain water such as water of crystallization, which may lead to reduced reproducibility. However, the present disclosure provides a method for producing a trifluoromethanesulfonyloxy compound with good reproducibility and excellent yield by using a non-nucleophilic strong base as the base.

[0022] The present disclosure will be described in detail below. Hereinafter, embodiments of the present disclosure will be described, but the present disclosure is not limited to the following embodiments and can be appropriately implemented based on the ordinary knowledge of those skilled in the art within the scope of the present disclosure.

[0023] <Trifluoromethanesulfonylating Agent Composition> (Trifluoromethanesulfonylating Agent) The trifluoromethanesulfonylating 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) as a trifluoromethanesulfonylating agent.

[0024]

[0025] In general formula (1), R １ is a hydrogen atom, a halogen atom, or an aliphatic hydrocarbon group having 1 to 6 carbon atoms; R ２ is a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms, and X is a nitrogen atom or C(R３ ), and Y is a nitrogen atom or C(R ４ ) and R ３ is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; ４ is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; ２ and R ３ may be bonded to form a ring, and R ２ and R ４ may be bonded to form a ring, and n is an integer of 1 to 3. ２ R when there are multiple ２ may be the same or different, R ３ R when there are multiple ３ may be the same or different.

[0026] In general formula (1), R １ represents a hydrogen atom, a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), or an aliphatic hydrocarbon group having 1 to 6 carbon atoms. The aliphatic hydrocarbon group may be linear, branched, or cyclic. When the hydrocarbon group is branched or cyclic, the aliphatic hydrocarbon group has 3 to 6 carbon atoms. Examples of the aliphatic hydrocarbon group include alkyl groups, alkenyl groups, and alkynyl groups, and any of these may be used, but alkyl groups are preferred. Examples of the alkyl group include linear alkyl groups having 1 to 6 carbon atoms, branched alkyl groups having 3 to 6 carbon atoms, and cyclic alkyl groups having 3 to 6 carbon atoms, and any of these may be used, but linear alkyl groups having 1 to 6 carbon atoms and branched alkyl groups having 3 to 6 carbon atoms are preferred.

[0027] Examples of linear alkyl groups having 1 to 6 carbon atoms include methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl groups. Examples of branched alkyl groups having 3 to 6 carbon atoms include isopropyl, isobutyl, sec-butyl, and tert-butyl groups. Examples of cyclic alkyl groups having 3 to 6 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups. In this specification, alkenyl and alkynyl groups include groups obtained by removing two and four hydrogen atoms, respectively, from an alkyl group.

[0028] R １ Among these, a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group is preferred because of ease of synthesis.

[0029] In general formula (1), R ２ represents a hydrogen atom, a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), an aliphatic hydrocarbon group having 1 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms. ２ R when there are multiple ２ may be the same or different. The aliphatic hydrocarbon group having 1 to 6 carbon atoms may be linear, branched, or cyclic. When the hydrocarbon group is branched or cyclic, the aliphatic hydrocarbon group has 3 to 6 carbon atoms. Examples of the aliphatic hydrocarbon group having 1 to 6 carbon atoms include linear aliphatic hydrocarbon groups having 1 to 6 carbon atoms, branched aliphatic hydrocarbon groups having 3 to 6 carbon atoms, and cyclic aliphatic hydrocarbon groups having 3 to 6 carbon atoms. Any of these may be used, but linear aliphatic hydrocarbon groups having 1 to 6 carbon atoms and branched aliphatic hydrocarbon groups having 3 to 6 carbon atoms are preferred.

[0030] 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. Examples of the linear alkyl group having 1 to 6 carbon atoms include R １Examples of the alkyl group include a linear alkyl group having 1 to 6 carbon atoms.

[0031] 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. Examples of the branched alkyl group having 3 to 6 carbon atoms include R １ Examples of the cyclic aliphatic hydrocarbon group having 3 to 6 carbon atoms include a cyclic alkyl group having 3 to 6 carbon atoms, a cyclic alkenyl group having 3 to 6 carbon atoms, and a cyclic alkynyl group having 3 to 6 carbon atoms. Examples of the cyclic alkyl group having 3 to 6 carbon atoms include R １ Examples of the cyclic alkyl group having 3 to 6 carbon atoms include those described in the above.

[0032] Examples of aromatic hydrocarbon groups having 6 to 14 carbon atoms include a phenyl group, a naphthyl group, an anthryl group, etc. Examples of aromatic heterocyclic groups having 3 to 14 carbon atoms include a pyrrole group, a pyrazine group, a pyrimidine group, a pyridazine group, etc.

[0033] R ２ 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, and more 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. ２ is preferably a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or a nitro group, and more preferably a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

[0034] In the general formula (1), X is a nitrogen atom or C(R ３ ), and Y is a nitrogen atom or C(R ４ ) R ３ represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms. ３ R when there are multiple ３ may be the same or different.

[0035] Examples of the aliphatic hydrocarbon group having 1 to 6 carbon atoms include a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, and a cyclic aliphatic hydrocarbon group having 3 to 6 carbon atoms. Any of these may be used, but a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms and a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms are preferred. Examples of the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a cyclic 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 3 to 14 carbon atoms include R ２ Examples of the alkyl group include a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a cyclic 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 3 to 14 carbon atoms.

[0036] R ３ 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.

[0037] R ４ represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms. ４ R when there are multiple ４ may be the same or different.

[0038] Examples of the aliphatic hydrocarbon group having 1 to 6 carbon atoms include a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, and a cyclic aliphatic hydrocarbon group having 3 to 6 carbon atoms. Any of these may be used, but a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms and a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms are preferred. Examples of the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a cyclic 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 3 to 14 carbon atoms include R ２Examples of the alkyl group include a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, a cyclic 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 3 to 14 carbon atoms.

[0039] R ４ 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.

[0040] In the general formula (1), X is C(R ３ ) and Y is preferably a nitrogen atom.

[0041] n is an integer of 1 to 3. n is preferably 1.

[0042] R ２ and R ３ may be bonded to form a ring. ２ and R ３ The ring formed by the bonding of R is not particularly limited, but examples thereof include aromatic hydrocarbon rings having 6 to 14 carbon atoms (e.g., naphthalene ring, anthracene ring) and aromatic heterocyclic rings having 6 to 14 carbon atoms. ２ and R ４ may be bonded to form a ring. ２ and 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 (e.g., a naphthalene ring, an anthracene ring) or an aromatic heterocyclic ring having 6 to 14 carbon atoms.

[0043] In the general formula (1), X is C(R ３ ) and R １ , R ２ , and R ３ are each independently a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group (preferably a hydrogen atom). Furthermore, it is more preferable that Y is a nitrogen atom and n is 1.

[0044] Examples of compounds represented by general formula (1) are shown below, but the compounds are not limited to these.

[0045]

[0046] The use of a trifluoromethanesulfonylating agent composition containing a compound represented by the above-described general formula (1) makes it possible to trifluoromethanesulfonylate a substrate having a phenolic hydroxyl group, etc., and one preferred aspect of the present disclosure is a trifluoromethanesulfonylating agent composition containing a compound represented by the above-described general formula (1) and a non-nucleophilic strong base. A trifluoromethanesulfonylating agent composition containing a compound represented by the general formula (1) and a specific base (hereinafter referred to as the trifluoromethanesulfonylating agent composition, or simply the composition) enables selective trifluoromethanesulfonylation of phenolic hydroxyl groups while suppressing the production of by-products. Furthermore, the trifluoromethanesulfonyloxy compound can be isolated from the reaction solution after the trifluoromethanesulfonylation reaction by simply performing a typical post-treatment procedure, allowing for industrially feasible and efficient production of the trifluoromethanesulfonyloxy compound. Furthermore, the inclusion of the specific base in the trifluoromethanesulfonylating agent composition makes it possible to provide a method for producing a trifluoromethanesulfonyloxy compound with good reproducibility and excellent yield.

[0047] In this specification, the phrase "selectively reacts" a trifluoromethanesulfonylation agent with a phenolic hydroxyl group means that the trifluoromethanesulfonylation reaction proceeds preferentially with the phenolic hydroxyl group. The composition of the present disclosure contains a compound represented by general formula (1). Two or more types of compounds represented by general formula (1) may be combined. The compound represented by general formula (1) preferably accounts for 80% or more, and more preferably 90% or more, of the total mass of the composition.

[0048] (Base) The trifluoromethanesulfonylating agent composition of the present disclosure contains a non-nucleophilic strong base. Two or more types of bases may be used in combination. Inorganic bases such as potassium carbonate have low solubility in reaction solvents and may contain water such as water of crystallization, which may lead to reduced reproducibility. However, the use of a non-nucleophilic strong base in the present disclosure is expected to result in good reproducibility and excellent yield.

[0049] In the present specification, a non-nucleophilic strong base refers to a base in which the nucleophilicity of the lone electron pair on the nitrogen atom is weak due to steric hindrance and the basicity (pKaH of a proton adduct of the non-nucleophilic strong base) is within the preferred numerical range described below.

[0050] The non-nucleophilic strong base is preferably a compound represented by the following general formula (A). (In general formula (A), R １００ ~R １０２ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; R １０３ represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 3 to 14 carbon atoms, or NR １０４ R １０５ and R １０４ , R １０５ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; R １００ and R １０１ may be bonded to form a ring, and R １０２ and R １０３ may be bonded to form a ring.)

[0051] R １００ ~R １０５ The hydrogen atom, the aliphatic hydrocarbon group having 1 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 3 to 14 carbon atoms are the same as those explained in the general formula (1). As the aliphatic hydrocarbon group having 1 to 6 carbon atoms, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms and a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms are preferred.

[0052] R １００ ~R １０２ is preferably a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, or a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, more preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, still more preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 3 carbon atoms, and particularly preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 2 carbon atoms. １０３ is NR １０４ R １０５ It is preferable that R １０４ , R １０５ is preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 3 carbon atoms, and even more preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 2 carbon atoms. As the linear aliphatic hydrocarbon group, a linear alkyl group is preferred.

[0053] In a more preferred embodiment, R １００ and R １０１ are bonded to form a ring, or R １０２ and R １０３ are preferably bonded to form a ring, and R １００ and R １０１ are bonded to form a ring, and R １０２ and R １０３ More preferably, R １００ and R １０１ are bonded to form a ring, and R １０２ and R １０３ When these are bonded to form a ring, the compound represented by the general formula (A) becomes a compound represented by the following general formula (A-1). (In general formula (A-1), R １０６ , R １０７ are each independently a divalent group.

[0054] R １００ and R １０１ A group formed by bonding (R １０６ ), R １０２ and R １０３ A group formed by bonding (R １０７) is not particularly limited as long as it is a divalent group, and examples thereof include divalent hydrocarbon groups which may contain heteroatoms. The number of carbon atoms in the hydrocarbon group is preferably 2 to 15, more preferably 3 to 10, and even more preferably 3 to 6.

[0055] Examples of the hydrocarbon group include an alkylene group, an alkenylene group, an alkynylene group, etc. Among these, an alkylene group is preferred.

[0056] Examples of the alkylene group include an ethylene group, a propylene group, a butylene group, a pentylene group, a hexylene group, a heptylene group, an octylene group, a nonylene group, a decylene group, etc. Among these, a propylene group, a butylene group, and a pentylene group are preferred.

[0057] Examples of the alkenylene group include a 1-propenylene group, a 2-propenylene group, a 1-butenylene group, a 2-butenylene group, a 1-pentenylene group, a 2-pentenylene group, a 1-hexenylene group, a 2-hexenylene group, and a 1-octenylene group.

[0058] Examples of the alkynylene group include an ethynylene group, a propynylene group, a butynylene group, a pentynylene group, a hexynylene group, a heptynylene group, an octynylene group, a nonynylene group, a decynylene group, an undecynylene group, and a dodecynylene group.

[0059] The hydrocarbon group may contain heteroatoms, but preferably does not contain heteroatoms, such as nitrogen atoms, oxygen atoms, sulfur atoms, halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms), and silicon atoms.

[0060] Regarding the compound represented by the general formula (A-1), R １０６ , R １０７ In the compound represented by the general formula (A), R １００ and R １０１ are bonded to form a ring, or R １０２ and R １０３ When R are bonded to form a ring, that is, when only one ring is formed, R １０６ , R １０７are the same as those in the case of the compound represented by the general formula (A-1), including preferred embodiments.

[0061] The compound represented by the general formula (A) is not particularly limited, and examples thereof include, in addition to compounds having a heterocyclic group having 4 or more carbon atoms described below, 1,1,3,3-tetramethylguanidine, 1,1,3,3-tetraethylguanidine, 1,1,3,3-tetrapropylguanidine, 1,1,3-trimethylguanidine, 1,3,3-trimethylguanidine, 1,1,3-triethylguanidine, 1,3,3-triethylguanidine, 1,1,3-tripropylguanidine, and 1,3,3-tripropylguanidine.

[0062] The non-nucleophilic strong base is preferably an organic base, more preferably a heterocyclic group-containing organic base, still more preferably a compound having a heterocyclic group with 4 or more carbon atoms, and particularly preferably a compound having a nitrogen atom and a heterocyclic group with 4 or more carbon atoms. Specific examples 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-collidine, 2,4,5-collidine, 2,5,6-collidine, 2,4,6-collidine, 3,4,5-collidine, and 3,5,6-collidine.

[0063] Use of the heterocyclic group-containing organic base tends to provide a method for producing a trifluoromethanesulfonyloxy compound with better reproducibility and excellent yield.

[0064] The higher the basicity of the non-nucleophilic strong base, the better the reproducibility and yield tend to be, and therefore the pKaH of the protonated product of the non-nucleophilic strong base is preferably 9.0 or more, more preferably 10.0 or more, even more preferably 11.0 or more, particularly preferably 12.0 or more, and most preferably 13.0 or more, and the upper limit is not particularly limited, but is, for example, 37.0 or less. The reason why the higher the basicity of the non-nucleophilic strong base, the better the reproducibility and yield tend to be is presumed to be as follows: The presence of a highly basic non-nucleophilic strong base generates phenoxide ions, which are generated by deprotonating the hydroxyl group of the aromatic hydroxyl compound represented by general formula (2), which has high acidity, and these phenoxide ions easily coexist. In this case, since the reactivity of the compound represented by general formula (1) is relatively low, the reaction proceeds preferentially with the most nucleophilic phenoxide ion present in the system. On the other hand, when the aromatic hydroxyl compound represented by general formula (2) has an amino group, the amino group is not deprotonated and remains as an amino group, and cannot react with the compound represented by general formula (1), which has relatively low reactivity. It is presumed that the presence of a highly basic non-nucleophilic strong base selectively deprotonates the hydroxyl group of the aromatic hydroxyl compound represented by general formula (2) to generate a phenoxide ion, resulting in a reaction that proceeds selectively at the hydroxyl group. In this specification, the pKaH of the proton adduct of a non-nucleophilic strong base is measured by dissolving the non-nucleophilic strong base in dimethyl sulfoxide (DMSO) at 25°C.

[0065] The non-nucleophilic strong base is preferably liquid at 25° C. Inorganic bases such as potassium carbonate are solid at 25° C. and therefore have low solubility in reaction solvents, which may lead to reduced reproducibility. However, by using a non-nucleophilic strong base (preferably a non-nucleophilic strong organic base) that is liquid at 25° C., the reaction system tends to become more homogeneous, making it possible to provide a method for producing a trifluoromethanesulfonyloxy compound that is more suitable, has good reproducibility, and is excellent in yield. In this specification, "liquid at 25° C." means a base that has fluidity at 25° C., and includes cream-like and paste-like bases.

[0066] Non-nucleophilic strong bases include 1,8-diazabicyclo[5.4.0]undecene (DBU) (pKaH = 13.9), 1,5-diazabicyclo[4.3.0]nonene (DBN) (pKaH = 13.4), 1,1,3,3-tetramethylguanidine (TMG) (pKaH = 13.6), 2-tert-butyl-1,1,3,3-tetramethylguanidine, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) (pKaH = 15.3), 7-methyl-1, It is preferably any one selected from the group consisting of 5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (pKaH = 14.8), imino-tris(dimethylamino)phosphorane (pKaH = 16.4), phosphazene base P1-t-Bu (pKaH = 15.7), phosphazene base P2-t-Bu, phosphazene base P4-t-Bu (pKaH = 30.25), and lithium diisopropylamide (LDA) (pKaH = 36, THF). Among these, 1,8-diazabicyclo[5.4.0]undecene (DBU) (pKaH = 13.9), 1,5-diazabicyclo[4.3.0]nonene (DBN) (pKaH = 13.4), or 1,1,3,3-tetramethylguanidine (TMG) (pKaH = 13.6) is preferred, and 1,8-diazabicyclo[5.4.0]undecene (DBU) (pKaH = 13.9) is particularly preferred. These bases can be used alone or in combination.

[0067] In the trifluoromethanesulfonylating agent composition of the present disclosure, the total content of non-nucleophilic strong bases, relative to 100 mol% of bases, is preferably 80 mol% or more, more preferably 90 mol% or more, even more preferably 95 mol% or more, particularly preferably 98 mol% or more, and most preferably 100 mol%, because the effects of the present disclosure can be more suitably obtained.

[0068] The amount of base used is not particularly limited, but is usually preferably 0.01 to 20 moles, more preferably 0.05 to 5 moles, per mole of the compound to be trifluoromethanesulfonylated, as described below.

[0069] The composition of the present disclosure may further contain a solvent. The solvent is not particularly limited as long as it dissolves the compound represented by the general formula (1) and the base, and examples thereof include the reaction solvents for trifluoromethanesulfonylation described below. The composition of the present disclosure may or may not contain a solvent.

[0070] <Method for Producing Trifluoromethanesulfonyloxy Compound> A method for producing a trifluoromethanesulfonyloxy compound using the composition of the present disclosure (hereinafter also referred to as a production method) includes a step of reacting the above-described trifluoromethanesulfonylating agent composition with a compound represented by the following general formula (2):

[0071] (Compound to be trifluoromethanesulfonated) The compound to be trifluoromethanesulfonylated with the trifluoromethanesulfonylating agent composition (hereinafter also referred to as the compound to be trifluoromethanesulfonated) is an aromatic hydroxyl compound represented by the following general formula (2):

[0072]

[0073] In formula (2), Ar represents an aromatic ring group or a substituted aromatic ring group.

[0074] In the aromatic ring hydroxyl compound represented by general formula (2), Ar represents an aromatic ring group or a substituted aromatic ring group. The aromatic ring group is not particularly limited, but may be monocyclic or polycyclic, and is preferably an aromatic ring group having 1 to 18 carbon atoms. Examples include aromatic hydrocarbon groups such as phenyl, naphthyl, and anthryl, and aromatic heterocyclic groups containing a heteroatom such as a nitrogen atom, oxygen atom, or sulfur atom, such as pyrrolyl (including nitrogen-protected forms), pyridyl, pyrazyl, pyrimidyl, pyridazyl, triazyl, furyl, thienyl, indolyl (including nitrogen-protected forms), indazolyl, quinolyl, carbazolyl, pyrrolopyridyl, benzofuryl, and benzothienyl. In the above general formula (2), it is preferable that Ar represents an aromatic ring group, and the aromatic ring group is an aromatic heterocyclic group.

[0075] The substituted aromatic ring group has any number and any combination of substituents on any carbon or nitrogen atom of the aromatic ring group. Such substituents include halogen atoms such as 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, C(CF ３ ) ２ OH group (including protected hydroxyl groups), lower alkoxy groups such as methoxy, ethoxy and propoxy groups, lower haloalkoxy groups such as fluoromethoxy, chloromethoxy and bromomethoxy groups, lower acyloxy groups such as formyloxy, acetyloxy, propionyloxy and butyryloxy groups, cyano group, lower alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl groups, methoxycarbonylmethyl group, ethoxycarbonylethyl group and propoxycarbonyl group, Examples of the substituent include lower alkoxycarbonyl lower alkyl groups such as phenylpropyl group, β-D-glucopyranoside group, phenyl group, naphthyl group, anthryl group, pyrrolyl group (including nitrogen-protected groups), pyridyl group, furyl group, thienyl group, indolyl group (including nitrogen-protected groups), quinolyl group, aromatic ring groups such as benzofuryl group and benzothienyl group, protected carboxyl groups, amino groups, protected amino groups, lower alkylamino groups, lower alkylamino lower alkyl groups, hydroxyl groups, protected hydroxyl groups, and X'-Ar'-OH group. These substituents may be further substituted, for example, with the substituents of "such substituents" above.

[0076] In the above general formula (2), it is preferable that Ar represents a substituted aromatic ring group, and the substituent of the substituted aromatic ring group is a lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a β-D-glucopyranoside group, an amino group, a lower alkylamino group, or a hydroxyl group.

[0077] X' in the X'-Ar'-OH group is C(CH ３ ) ２ group, C (CF ３ ) ２group, oxygen atom, nitrogen atom (including nitrogen-protected atoms), sulfur atom, SO group or SO ２ group, and Ar' represents a phenylene group or a substituted phenylene group. The substitution position of the phenylene group is the 2-, 3-, or 4-position relative to the hydroxyl group. The substituents of the substituted phenylene group are the same as the substituents of the substituted aromatic ring group described above. Specific examples of aromatic hydroxyl compounds represented by general formula (2) substituted with an X'-Ar'-OH group include the following compounds.

[0078]

[0079] In this specification, "lower" means a straight or branched chain or cyclic (when the number of carbon atoms is 3 or more) group having 1 to 6 carbon atoms. The aromatic ring group in the above "substituents" includes halogen atoms, lower alkyl groups, lower unsaturated groups, lower haloalkyl groups, C(CF ３ ) ２ Substitution can also be made with an OH group (including a protected hydroxyl group), 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 protected carboxyl group, a protected amino group, a hydroxyl group, a protected hydroxyl group, an X'-Ar'-OH group, etc. Furthermore, protecting groups for pyrrolyl, indolyl, hydroxyl, carboxyl, and amino groups are protecting groups described in Protective Groups in Organic Synthesis, Third Edition, 1999, John Wiley & Sons, Inc., etc. Among these, aromatic ring groups and substituted aromatic ring groups excluding "hydroxyl groups", "aromatic ring groups" and "X'-Ar'-OH groups" as substituents are preferred, and aromatic hydrocarbon groups and substituted aromatic hydrocarbon groups (aromatic hydrocarbon groups having a substituent) excluding "hydroxyl groups", "aromatic ring groups" and "X'-Ar'-OH groups" as substituents are particularly preferred. In aromatic ring hydroxyl compounds having multiple hydroxyl groups, multiple fluorosulfonylation reactions may proceed depending on the reaction conditions employed.

[0080] In a preferred embodiment, the aromatic ring hydroxyl compound represented by the general formula (2) has at least one substituent selected from an alcoholic hydroxyl group and an amino group. These substituents may be further substituted, for example, with the substituents described above as "such substituents."

[0081] Examples of compounds represented by formula (2) are shown below, but the compounds are not limited to these.

[0082]

[0083] In the trifluoromethanesulfonylation reaction, the aromatic hydroxyl 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, per 1.0 mol of the trifluoromethanesulfonyl compound represented by the general formula (1).

[0084] (Solvent) The above-mentioned trifluoromethanesulfonylation reaction is preferably carried out using a reaction solvent. 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.

[0085] 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. Aliphatic hydrocarbon solvents include n-hexane, n-heptane, n-pentane, n-nonane, and n-decane. Aromatic hydrocarbon solvents include toluene, xylene, mesitylene, and ethylbenzene. Halogenated hydrocarbon solvents include methylene chloride, chloroform, and 1,2-dichloroethane. Ester solvents include ethyl acetate, isopropyl acetate, n-butyl acetate, and γ-butyrolactone. Amide solvents include N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone. Examples of nitrile solvents include acetonitrile, propionitrile, and benzonitrile. Examples of sulfoxide solvents include dimethyl sulfoxide. Among these, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, acetonitrile, propionitrile, and dimethyl sulfoxide are preferred because they are easily available and have excellent solubility for the substrate and the trifluoromethanesulfonylating agent of the present disclosure, and tetrahydrofuran, N,N-dimethylformamide, and acetonitrile are particularly preferred. These reaction solvents can be used alone or in combination.

[0086] The amount of the reaction solvent used for trifluoromethanesulfonylation is not particularly limited, but it is sufficient to use 0.05 L (liters) or more per mole of the compound to be trifluoromethanesulfonated, and usually 0.1 to 20 L is preferred, and particularly 0.1 to 10 L is more preferred.

[0087] (Reaction Temperature) The reaction temperature for trifluoromethanesulfonylation is not particularly limited, but is preferably 150°C or lower, more preferably in the range of -100 to 150°C, and even more preferably -78 to 100°C.

[0088] (Reaction Time) The reaction time for trifluoromethanesulfonylation is not particularly limited, but may be in the range of 0.1 to 72 hours. Since the reaction time varies depending on the raw materials and reaction conditions, it is preferable to follow the progress of the reaction by analytical means such as gas chromatography, liquid chromatography, or NMR, and determine the end point as the time when the raw materials have almost completely disappeared.

[0089] (Post-Treatment Procedure: Liquid Separation) After the above reaction, post-treatment procedures for isolating the trifluoromethanesulfonyloxy compound may be carried out using procedures commonly used in organic synthesis. For example, it is preferable to post-treat the reaction solution containing the trifluoromethanesulfonyloxy compound after the completion of the reaction with water, an acidic aqueous solution, or an alkaline aqueous solution. That is, the reaction solution after the completion of the reaction may be 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) may be concentrated. Examples of organic solvents for post-treatment include ether solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, and ester solvents.

[0090] Specific examples of organic solvents 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, methylene chloride, chloroform, 1,2-dichloroethane, ethyl acetate, and n-butyl acetate. Among these, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, 2-methyltetrahydrofuran, cyclopentyl methyl ether, toluene, xylene, mesitylene, ethylbenzene, methylene chloride, chloroform, 1,2-dichloroethane, ethyl acetate, and n-butyl acetate are preferred, with ethyl acetate being particularly preferred. These reaction solvents can be used alone or in combination.

[0091] The amount of solvent used in the post-treatment is not particularly limited, but it is sufficient to use 0.05 L (liters) or more per mole of the compound to be trifluoromethanesulfonylated, and usually 0.1 to 20 L is preferred, and 0.1 to 10 L is more preferred.

[0092] Specific examples of mineral acids for post-treatment include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and nitric acid. Among these, hydrochloric acid and sulfuric acid are preferred, with hydrochloric acid being particularly preferred. Specific examples of alkali metal salts for post-treatment include sodium bicarbonate, potassium bicarbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, and potassium carbonate.

[0093] The obtained trifluoromethanesulfonyloxy compound can be suitably used, for example, in a coupling reaction using a transition metal, etc. As described above, the trifluoromethanesulfonyloxy compound obtained by the production method of the present disclosure can be isolated from the reaction solution after completion of the reaction by simply performing a simple post-treatment operation, making it industrially feasible, and as a result, it becomes possible to produce a coupling reaction product much more efficiently than by conventional methods.

[0094] The present disclosure will be described in detail below with reference to examples, but the present disclosure is not limited to these examples. In the examples and comparative examples, the yield (%) refers to the percentage of the product obtained by the nuclear magnetic resonance spectrum １ H-NMR or １９ F-NMR analysis confirmed the internal standard method ( １ In the H-NMR analysis, 1,4-bistrimethylsilylbenzene was used as an internal standard. １９ In the F-NMR analysis, the value was obtained by quantifying using benzotrifluoride as an internal standard substance.

[0095] Example 1: 109 mg (1.00 mmol, 1.0 eq.) of p-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, a composition containing both components, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.2 eq.) of 1,8-diazabicyclo[5.4.0]undecene (DBU), was added to the reactor and stirred at 50°C for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The solution was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate, and the quantitative yield was 96%.

[0096] [Physical properties] 4-aminophenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.04 (d, J=9.1 Hz, 2H), 6.65 (d, J=9.1 Hz, 2H), 3.80 (s, 2H). １９ F-NMR (376MHz, CDCl ３) δ: -72.6 (3F).

[0097] The reaction in Example 1 is shown below. Similar reactions also proceed in Examples 2 to 5 and Comparative Example 1, but in Example 2 and Comparative Example 1, 1,1,3,3-tetramethylguanidine and potassium carbonate are used, respectively, instead of 1,8-diazabicyclo[5.4.0]undecene (DBU).

[0098]

[0099] Example 2: 109 mg (1.00 mmol, 1.0 eq.) of p-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, a composition containing both components, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 23.0 mg (0.20 mmol, 0.2 eq.) of 1,1,3,3-tetramethylguanidine, was added to the reactor and stirred at 50°C for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The solution was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate, and the quantitative yield was 96%.

[0100] Comparative Example 1: 109 mg (1.00 mmol, 1.0 eq.) of p-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, a composition containing both components, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 27.6 mg (0.20 mmol, 0.2 eq.), was added to the reactor and stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of tap water, and the layers were separated. The resulting aqueous phase was further extracted twice with 20 mL of dichloromethane, and the entire resulting organic phase was dried over sodium sulfate. To the resulting residue, 1,4-bistrimethylsilylbenzene was added as an internal standard. １ Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate. Similar experiments were carried out four times, and the quantitative yields were as shown in Table 1 below.

[0101] Example 3: 109 mg (1.00 mmol, 1.0 eq.) of p-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.2 eq.) of 1,8-diazabicyclo[5.4.0]undecene (DBU) were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The solution was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate. Similar experiments were carried out four times, and the quantitative yields were as shown in Table 1 below.

[0102]

[0103] From Table 1, it can be seen that when a non-nucleophilic strong base such as DBU is used, excellent yields are obtained with good reproducibility.

[0104] Example 4: 109 mg (1.00 mmol, 1.0 eq.) of p-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 1.5 mg (0.01 mmol, 0.01 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The solution was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate, and the quantitative yield was 99%.

[0105] Example 5: 2.18 g (20.0 mmol, 1.0 eq.) of p-aminophenol as the substrate and 100 mL of acetonitrile as the reaction solvent were collected and placed in a 300 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 4.40 g (22.0 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.01 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 100 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 100 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The mixture was then transferred to a separatory funnel with 100 mL of dichloromethane and 100 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 100 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate, and the quantitative yield was 94%.

[0106] Example 6: 133 mg (1.00 mmol, 1.0 eq.) of 5-hydroxyindole as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 440 mg (1.10 mmol, 2.2 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １Analysis by H-NMR confirmed a signal derived from 1-trifluoromethanesulfonyl-1H-indol-5-yl trifluoromethanesulfonate, and the quantitative yield was 95%.

[0107] [Physical properties] 1-trifluoromethanesulfonyl-1H-indol-5-yl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.98 (d, J=9.1Hz, 1H), 7.59 (d, J=2.5Hz, 1H), 7.51 (d, J=3.8Hz, 1H), 7.33 (dd, J=9.1, 2.6Hz, 1H), 6.89 (d, J=3.9Hz, 1H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.5, -75.2.

[0108] The reaction in Example 6 is shown below.

[0109]

[0110] Example 7: 137 mg (1.00 mmol, 1.0 eq.) of tyramine as a substrate and 5 mL of acetonitrile as a reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer. Subsequently, a composition containing both components, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene, was added to the reactor and stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution to adjust the pH to 7, after which the solution was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water and separated into layers. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-(2-aminoethyl)phenyl trifluoromethanesulfonate, and the quantitative yield was 81%.

[0111] [Physical properties] 4-(2-aminoethyl)phenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.26 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 2.96 (t, J = 6.9 Hz, 2H), 2.76 (t, J = 6.9 Hz, 2H), 1.33 (s, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.7 (3F).

[0112] The reaction in Example 7 is shown below.

[0113]

[0114] Example 8: 138 mg (1.00 mmol, 1.0 eq.) of 4-(2-hydroxyethyl)phenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 15.2 mg (0.10 mmol, 0.10 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-(2-hydroxyethyl)phenyl trifluoromethanesulfonate, and the quantitative yield was 85%.

[0115] [Physical properties] 4-(2-hydroxyethyl)phenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl３ ) δ: 7.29 (d, J=8.9Hz, 2H), 7.20 (d, J=8.9Hz, 2H), 3.80 (t, J=6.6Hz, 2H), 2.85 (t, J=6.5Hz, 2H), 2.21 (s, 1H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.9 (3F).

[0116] The reaction in Example 8 is shown below.

[0117]

[0118] Comparative Example 2: 168 mg (1.00 mmol, 1.0 eq.) of methyl 3,4-dihydroxybenzoate as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, a composition containing both components, 310 mg (1.10 mmol, 1.1 eq.) of trifluoromethanesulfonic acid anhydride and 223 mg (2.20 mmol, 2.20 eq.), was added to the reactor and stirred at room temperature for 30 minutes to obtain a reaction solution. 5 mL of saturated aqueous sodium bicarbonate was added to the reaction solution, which was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water for layer separation. The resulting aqueous phase was further extracted twice with 20 mL of dichloromethane, and the entire resulting organic phase was dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the resulting residue as an internal standard, and the resulting solution was separated. １ Analysis by H-NMR confirmed signals derived from methyl 4-hydroxy-3-trifluoromethanesulfonylbenzoate and methyl 3,4-bistrifluoromethanesulfonylbenzoate, and the quantitative yields were 33% and 32%, respectively.

[0119] [Physical properties] Methyl 4-hydroxy-3-trifluoromethanesulfonylbenzoate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.29 (d, J=8.9Hz, 2H), 7.20 (d, J=8.9Hz, 2H), 3.80 (t, J=6.6Hz, 2H), 2.85 (t, J=6.5Hz, 2H), 2.21 (s, 1H). １９ F-NMR (376MHz, CDCl ３) δ: -72.9 (3F). 3,4-bistrifluoromethanesulfonylbenzoic acid methyl ester; １ H-NMR (400MHz, CDCl ３ ) δ: 8.17 (dd, J=8.6, 2.0Hz, 1H), 8.14 (d, J=1.9Hz, 1H), 7.58 (d, J=8.7Hz, 1H), 3.98 (s, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.9 (6F).

[0120] Example 9: 168 mg (1.00 mmol, 1.0 eq.) of methyl 3,4-dihydroxybenzoate as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 48 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution, adjusting the pH to 7. The mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed signals derived from methyl 4-hydroxy-3-trifluoromethanesulfonylbenzoate and methyl 3,4-bistrifluoromethanesulfonylbenzoate, and the quantitative yields were 56% and 3%, respectively.

[0121] The reaction in Example 9 is shown below.

[0122]

[0123] Example 10: 109 mg (1.00 mmol, 1.0 eq.) of p-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 1.5 mg (0.01 mmol, 0.01 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-aminophenyl trifluoromethanesulfonate, and the quantitative yield was 96%.

[0124] [Physical properties] 4-aminophenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.04 (d, J=9.1 Hz, 2H), 6.65 (d, J=9.1 Hz, 2H), 3.80 (s, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.6 (3F).

[0125] The reaction in Example 10 is shown below.

[0126]

[0127] Example 11: 109 mg (1.00 mmol, 1.0 eq.) of m-aminophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 1.5 mg (0.01 mmol, 0.01 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 3-aminophenyl trifluoromethanesulfonate, and the quantitative yield was 82%.

[0128] [Physical properties] 3-aminophenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.18 (t, J=8.2Hz, 1H), 6.70-6.59 (m, 2H), 6.55 (t, J=2.3Hz, 2H), 3.88 (s, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.9 (3F).

[0129] The reaction in Example 11 is shown below.

[0130]

[0131] [Example 12]

[0132] 185 mg (1.00 mmol, 1.0 eq.) of 4-(phenylamino)phenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as the reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the resulting mixture was stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was then stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-(phenylamino)phenyl trifluoromethanesulfonate, and the quantitative yield was 100%.

[0133] [Physical properties] 4-(phenylamino)phenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.39-7.22 (m, 2H), 7.18-6.96 (m, 7H), 5.80 (s, 1H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.6 (3F).

[0134] The reaction in Example 12 is shown below.

[0135] Example 13: 209 mg (1.00 mmol, 1.0 eq.) of tert-butyl (2-hydroxyphenyl) carbamate as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, and the mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 2-((tert-butoxycarbonyl)amino)phenyl trifluoromethanesulfonate, and the quantitative yield was 75%.

[0136] [Physical properties] 2-((tert-butoxycarbonyl)amino)phenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 8.09 (d, J=8.1Hz, 1H), 7.40-7.23 (m, 2H), 7.10 (m, 1H), 6.67 (s, 1H), 1.53 (s, 9H). １９ F-NMR (376MHz, CDCl ３ ) δ: -73.3 (3F).

[0137] The reaction in Example 13 is shown below.

[0138]

[0139] Example 14: 151 mg (1.00 mmol, 1.0 eq.) of N-(4-hydroxyphenyl)acetamide as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-acetamidophenyl trifluoromethanesulfonate, and the quantitative yield was 100%.

[0140] [Physical properties] 4-acetamidophenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.64-7.57 (d, J=9.0Hz, 2H), 7.30 (s, 1H), 7.24 (d, J=9.0Hz, 2H), 2.21 (s, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.7 (3F).

[0141] The reaction in Example 14 is shown below.

[0142]

[0143] Example 15: 143 mg (0.50 mmol, 1.0 eq.) of 2'-amino-[1,1'-binaphthalen]-2-ol as the substrate and 2.5 mL of acetonitrile as the reaction solvent were collected and placed in a 10 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 110 mg (0.55 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 3.8 mg (0.025 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, and the mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 2'-amino-[1,1'-binaphthalen]-2-yl trifluoromethanesulfonate, and the quantitative yield was 62%.

[0144] [Physical properties] 2'-amino-[1,1'-binaphthalen]-2-yl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 8.08 (d, J = 9.0 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.82 (dd, J = 23.0, 8.3 Hz, 2H), 7.62-7.54 (m, 2H), 7. 52-7.41 (m, 2H), 7.29-7.17 (m, 2H), 7.12 (dd, J=8.7, 1.3Hz, 1H), 6.90 (d, J=8.2Hz, 1H), 3.40 (s, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ: -74.3 (3F).

[0145] The reaction in Example 15 is shown below.

[0146]

[0147] Example 16: 95.1 mg (1.00 mmol, 1.0 eq.) of 3-hydroxypyridine as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, and the mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from pyridin-3-yl trifluoromethanesulfonate, and the quantitative yield was 50%.

[0148] [Physical properties] Pyridin-3-yl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 8.67 (d, J = 4.7 Hz, 1H), 8.62 (d, J = 2.9 Hz, 1H), 7.66 (m, 2.5, 1H), 7.45 (m, 1H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.5 (3F).

[0149] The reaction in Example 16 is shown below.

[0150]

[0151] Example 17: 145 mg (1.00 mmol, 1.0 eq.) of 6-quinolinol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, and the mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from quinolin-6-yl trifluoromethanesulfonate, and the quantitative yield was 79%.

[0152] [Physical properties] Quinolin-6-yl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 9.01 (dt, J = 4.2, 1.4 Hz, 1H), 8.25-8.18 (m, 2H), 7.77 (d, J = 2.7 Hz, 1H), 7.62 (dd, J=9.2, 2.8Hz, 1H), 7.52 (dd, J=8.3, 4.2Hz, 1H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.5 (3F).

[0153] The reaction in Example 17 is shown below.

[0154]

[0155] Example 18: 124 mg (1.00 mmol, 1.0 eq.) of 4-methoxyphenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene (a composition containing both components) were added to the reactor and stirred at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, after which the solution was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water and separated into layers. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-methoxyphenyl trifluoromethanesulfonate, and the quantitative yield was 81%.

[0156] [Physical properties] 4-Methoxyphenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.19 (d, J = 9.1 Hz, 2H), 6.91 (d, J = 9.6 Hz, 2H), 3.80 (s, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.7 (3F).

[0157] The reaction in Example 18 is shown below.

[0158]

[0159] Example 19: 140 mg (1.00 mmol, 1.0 eq.) of 4-(methylthio)phenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at room temperature for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-(methylthio)phenyl trifluoromethanesulfonate, and the quantitative yield was 99%.

[0160] [Physical properties] 4-(methylthio)phenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.33-7.24 (m, 2H), 7.23-7.15 (m, 2H), 2.49 (s, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.6 (3F).

[0161] The reaction in Example 19 is shown below.

[0162]

[0163] Example 20: 152 mg (1.00 mmol, 1.0 eq.) of methyl 4-hydroxybenzoate as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, followed by stirring at 60°C for 2 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and then the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, after which the mixture was transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from methyl 4-(trifluoromethanesulfonyloxy)benzoate, and the quantitative yield was 93%.

[0164] [Physical properties] Methyl 4-(trifluoromethanesulfonyloxy)benzoate; １ H-NMR (400MHz, CDCl ３ ) δ: 8.20-8.10 (m, 2H), 7.41-7.31 (m, 2H), 3.95 (s, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.6 (3F).

[0165] The reaction in Example 20 is shown below.

[0166]

[0167] Example 21: 162 mg (1.00 mmol, 1.0 eq.) of 4-(trifluoromethyl)phenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 24 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, and the mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from methyl 4-(trifluoromethanesulfonyloxy)benzoate, and the quantitative yield was 53%.

[0168] [Physical properties] 4-(trifluoromethyl)phenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.76 (d, J = 9.0 Hz, 2H), 7.42 (d, J = 9.0 Hz, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.6 (6F).

[0169] The reaction in Example 21 is shown below.

[0170]

[0171] Example 22: 139 mg (1.00 mmol, 1.0 eq.) of 4-nitrophenol as the substrate and 5 mL of acetonitrile as the reaction solvent were collected and placed in a 30 mL eggplant-shaped flask equipped with a stirrer, which served as a reactor. Subsequently, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene were added to the reactor, and the mixture was stirred at room temperature for 24 hours to obtain a reaction solution. 5 mL of 1 mol / L hydrochloric acid was added to the reaction solution to adjust the pH to 1, and the mixture was stirred at room temperature for 5 minutes. 5 mL of 1 mol / L aqueous sodium bicarbonate solution was added to the resulting solution to adjust the pH to 7, and the mixture was then transferred to a separatory funnel with 20 mL of dichloromethane and 20 mL of clean water, and the layers were separated. The obtained aqueous phase was further extracted twice with 20 mL of dichloromethane, and all the obtained organic phases were dried over sodium sulfate. 1,4-bistrimethylsilylbenzene was added to the obtained residue as an internal standard, １ Analysis by H-NMR confirmed a signal derived from 4-nitrophenyl trifluoromethanesulfonate, and the quantitative yield was 58%.

[0172] [Physical properties] 4-nitrophenyl trifluoromethanesulfonate; １ H-NMR (400MHz, CDCl ３ ) δ: 7.76 (d, J = 9.0 Hz, 2H), 7.42 (d, J = 9.0 Hz, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ: -72.4 (6F).

[0173] The reaction in Example 22 is shown below.

[0174]

[0175] Example 23: 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 collected and placed in a 30 mL recovery flask equipped with a stirrer, which served as a reactor. Subsequently, a composition containing both components, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 7.6 mg (0.05 mmol, 0.05 eq.) of 1,8-diazabicyclo[5.4.0]undecene, was added to the reactor and stirred at room temperature for 2 hours to obtain a reaction solution. Benzotrifluoride was added to the reaction solution as an internal standard, and １９ Analysis by F-NMR confirmed a signal at -74 ppm derived from methyl 2-amino-3-(4-trifluoromethanesulfonyloxyphenyl)propanoate, and the quantitative yield was 84%.

[0176] The reaction in Example 23 is shown below.

[0177]

[0178] Example 24: 273 mg (1.00 mmol, 1.0 eq.) of arbutin as a substrate and 5 mL of dimethylformamide as a reaction solvent were collected and placed in a 30 mL recovery flask equipped with a stirrer, which served as a reactor. Subsequently, a composition containing both components, 220 mg (1.10 mmol, 1.1 eq.) of 1-trifluoromethanesulfonylimidazole and 30.4 mg (0.20 mmol, 0.20 eq.) of 1,8-diazabicyclo[5.4.0]undecene, was added to the reactor and stirred at room temperature for 4 hours to obtain a reaction solution. Benzotrifluoride was added to the reaction solution as an internal standard, and １９ F-NMR analysis confirmed a signal at -74 ppm derived from 4-trifluoromethanesulfonyloxyphenyl β-D-glucopyranoside, and the quantitative yield was 81%.

[0179] The reaction in Example 24 is shown below.

[0180]

[0181] The trifluoromethanesulfonylating agent composition of the present disclosure can be used as a trifluoromethanesulfonylating agent composition in the synthesis of pharmaceutical active ingredients or intermediates under industrially feasible conditions.

[0182] Although the present disclosure has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the disclosure.

Claims

1. A trifluoromethanesulfonylating agent composition comprising a compound represented by the following general formula (1) and a non-nucleophilic strong base: (In general formula (1), R １ is a hydrogen atom, a halogen atom, or an aliphatic hydrocarbon group having 1 to 6 carbon atoms; R ２ is a hydrogen atom, a halogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, a nitro group, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; X is a nitrogen atom or C(R ３ ), and Y is a nitrogen atom or C(R ４ ) and R ３ is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; ４ is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; ２ and R ３ may be bonded to form a ring, R ２ and R ４ may be bonded to form a ring, and n is an integer of 1 to 3. ２ R when there are multiple ２ may be the same or different, R ３ R when there are multiple ３ may be the same or different.) 2. The trifluoromethanesulfonylating agent composition according to claim 1, wherein the non-nucleophilic strong base is a compound represented by the following general formula (A): (In general formula (A), R １００ ~R １０２ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; R １０３ represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 3 to 14 carbon atoms, or NR １０４ R １０５ and R １０４ , R １０５ are each independently a hydrogen atom, an aliphatic hydrocarbon group having 1 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 3 to 14 carbon atoms; R １００ and R １０１ may be bonded to form a ring, R １０２ and R １０３ may be bonded to form a ring.) 3. In the general formula (1), X is C(R ３ ) and R １ , R ２ , and R ３ The trifluoromethanesulfonylating agent composition according to claim 1, wherein each of independently represents a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

4. The trifluoromethanesulfonylating agent composition according to claim 1, wherein the non-nucleophilic strong base is a compound having a heterocyclic group having a nitrogen atom and 4 or more carbon atoms.

5. The trifluoromethanesulfonylating agent composition according to claim 1, wherein the non-nucleophilic strong base is 1,8-diazabicyclo[5.4.0]undecene, 1,5-diazabicyclo[4.3.0]nonene, or 1,1,3,3-tetramethylguanidine.

6. The trifluoromethanesulfonylating agent composition according to any one of claims 1 to 5, (wherein, Ar represents an aromatic ring group or a substituted aromatic ring group) with an aromatic hydroxyl compound represented by the following general formula (2):

7. The method for producing a trifluoromethanesulfonyloxy compound according to claim 6, wherein, in said general formula (2), Ar represents an aromatic ring group, and said aromatic ring group is an aromatic heterocyclic group.

8. The method for producing a trifluoromethanesulfonyloxy compound according to claim 6, wherein in said general formula (2), Ar represents a substituted aromatic ring group, and the substituted aromatic ring group has a substituent which is a lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a β-D-glucopyranoside group, an amino group, a lower alkylamino group, or a hydroxyl group.

9. The method for producing a trifluoromethanesulfonyloxy compound according to claim 6, wherein the reaction is carried out at a reaction temperature of 150° C. or less.

10. The method for producing a trifluoromethanesulfonyloxy compound according to claim 6, wherein the reaction solution after completion of the reaction is post-treated with an acidic aqueous solution.

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