Amino group eliminating agent, reaction product production method, reaction precursor, reaction precursor production method, and method for producing optically active reaction product

Abstract

This amino group eliminating agent is for producing a reaction product by causing an organic compound having an amino group to react with the amino group eliminating agent and then to react with a nucleophile, and comprises a compound (a) represented by formula (a).　(a): Y1-X1-Rf-X2-Y2 In formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group including at least one fluorine atom, X1 and X2 each independently represent a carbonyl group or a sulfonyl group, and Y1 and Y2 each independently represent a halogen atom or the like.

Description

Amino group leaving group agent, method for producing reaction product, reaction precursor, method for producing reaction precursor, and method for producing optically active reaction product

[0001] The present invention relates to an amino group leaving group-forming agent, a method for producing a reaction product, a reaction precursor, a method for producing a reaction precursor, and a method for producing an optically active reaction product. This application claims priority based on Japanese Patent Application No. 2023-120055, filed on July 24, 2023, the contents of which are incorporated herein by reference.

[0002] An amino group (NH ２ Primary alkylamines bearing an amino group (C-N bond) are commonly found in natural products such as amino acids and alkaloids, as well as in commercially available organic compounds and compound libraries for pharmaceutical synthesis, and are known as one of the most readily available compounds. Structures with an amino group on the alkyl group are also frequently found in pharmaceuticals, pesticides, electronic materials, functional materials, and their raw materials and intermediates. When synthesizing desired organic compounds, reactions that convert a target functional group to a desired functional group are extremely useful. However, reactions that directly convert an amino group on an alkyl carbon to another functional group are considered more difficult than reactions that convert halogen substituents or hydroxyl groups, etc. This is due to the strong bond energy of the C-N bond and the inherent basicity of amines.

[0003] For example, the Sandmeyer reaction is a classic method for converting an amino group into another functional group. This involves converting the amino group into a diazo group and then introducing a substituent such as chlorine, bromine, or iodine. While this reaction proceeds efficiently with aromatic amines, it is difficult to apply to aliphatic amines. Several functionalization reactions for aliphatic amines have been developed (Non-Patent Document 1), including a method of converting the amino group into a pyridinium salt followed by functionalization (Non-Patent Documents 2 and 3), and a method of converting the amino group into an isodiazene by reacting it with an anomeric amide and then releasing the nitrogen molecule to functionalize it (Non-Patent Documents 4 and 5). Other reagents that convert amino groups into azide groups, such as trifluoromethanesulfonyl azide and fluorosulfuryl azide, have also been developed (Non-Patent Documents 6 and 7).

[0004] Kathleen J. Berger; Mark D. Levin. Organic & Biomolecular Chemistry (2020), 19, 11-36.Namek F. EWEISS; Alan R. KATRITZKY; Pai-Lin NIE, Christopher A. RAMSDEN. Synthesis (1977), 9, 634-635.Felix J. R. Klauck; Michael J. James; Frank Glorius. Angewwandte Chemie International Edition (2017), 56(40), 12336-12339.Jiang-Hao Xue; Yin Li; Dong-Hang Tan; Fang-Hai Tu; Yuan Liu; Qingjiang Li; Honggen Wang. iScience (2023), 26(c), 106255.Balu D. Dherange; Mingbin Yuan; Christopher B. Kelly; Christopher A. Reiher; Cristina Grosanu; Kathleen J. Berger; Osvaldo Gutierrez; Mark D. Levin. Journal of the American Chemical Society (2023), 145(a), 17-24.C. J. Cavender; V. J. Shiner Jr. The Journal of Organic Chemistry (1972), 37(22), 3567-3569.Genyi Meng; Taijie Guo; Tiancheng Ma; Jiong Zhang; Yucheng Shen; Karl Barry Sharpless; Jiajia Dong. Nature (2019), 574, 86-89.

[0005] The functionalization reaction of primary alkylamines is a useful method for converting amino groups, but for example, the reaction via pyridinium salts described in Non-Patent Documents 2 and 3 may require high temperatures of 200 to 300°C or expensive transition metal catalysts. The method using anomeric amides described in Non-Patent Documents 4 and 5 raises safety concerns when scaling up, as some anomeric amides are decomposable. The reaction converting amino groups to azide groups described in Non-Patent Documents 6 and 7 requires the prior synthesis of trifluoromethanesulfonyl azide or fluorosulfuryl azide.

[0006] The present invention has been made in view of the above circumstances, and aims to provide an amino leaving group agent for efficiently producing a reaction product by reacting an organic compound having an amino group with an amino leaving group agent and then reacting the organic compound with a nucleophile, a method for producing a reaction product, a reaction precursor, a method for producing a reaction precursor, and a method for producing an optically active reaction product.

[0007] As a result of intensive research into the above-mentioned problems, the inventors of the present invention have found that a reaction product can be efficiently produced by reacting an organic compound having an amino group with a specific amino group leaving agent and then reacting the compound with a nucleophile, and have completed the present invention.

[0008] The present invention has the following features: [1] An amino leaving agent containing a compound (a) represented by the following formula (a), for producing a reaction product by reacting the amino leaving agent with an organic compound having an amino group, and then reacting the organic compound with a nucleophile: Y １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0009] [2] The amino leaving group-forming agent according to [1], wherein the organic compound is represented by the following formula (b): In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0010] [3] The amino leaving group generating agent according to [1] or [2], wherein the nucleophilic agent is used to substitute the amino group that has reacted with the amino leaving group generating agent with a chemical species, and the chemical species includes at least one selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, and a substituted or unsubstituted hydrocarbon group.

[0011] [4] The amino leaving group-forming agent according to any one of [1] to [3], wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２and R ３ at least two of these may be bonded to each other to form a ring; and Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

[0012] [5] A method for producing a reaction product, comprising reacting an amino group-containing organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a), and further reacting the compound with a nucleophile: １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0013] [6] The method for producing a reaction product according to [5], wherein the organic compound is represented by the following formula (b): In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0014] [7] The method for producing a reaction product according to [5] or [6], wherein the nucleophilic agent is used to substitute the amino group that has reacted with the amino group leaving group agent with a chemical species, and the chemical species comprises at least one selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, and a substituted or unsubstituted hydrocarbon group.

[0015] [8] The method for producing the reaction product according to any one of [5] to [7], wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; and Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

[0016] [9] A reaction precursor comprising a compound (e) represented by the following formula (e) or a compound (f) represented by the following formula (f) for obtaining a reaction product by reacting with a nucleophile: In the above formulas (e) and (f), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y ２ is a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group; M １ is a hydrogen atom or a counter ion; R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0017]

[10] The reaction precursor according to [9], wherein the nucleophilic agent is used to substitute the tertiary amino group in the above formulae (e) and (f) with a chemical species, and the chemical species includes at least one chemical species selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, and a substituted or unsubstituted hydrocarbon group.

[0018]

[11] The reaction precursor according to [9] or

[10] , wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; and Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

[0019]

[12] A method for producing a reaction precursor containing a compound (e) represented by the following formula (e) or a compound (f) represented by the following formula (f) for obtaining a reaction product by reacting with a nucleophile, the method comprising reacting an amino group-containing organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a): １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group. In the above formulas (e) and (f), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２are each independently a carbonyl group or a sulfonyl group; Y ２ is a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group; M １ is a hydrogen atom or a counter ion; R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0020]

[13] The method for producing a reaction precursor according to

[12] , wherein the organic compound is represented by the following formula (b): In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0021]

[14] The method for producing a reaction precursor according to

[12] or

[13] , wherein the nucleophilic agent is used to substitute the amino group that has reacted with the amino group leaving group agent with a chemical species, and the chemical species includes at least one chemical species selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, and a substituted or unsubstituted hydrocarbon group.

[0022]

[15] The method for producing a reaction precursor according to any one of

[12] to

[14] , wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; and Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

[0023]

[16] A method for producing an optically active reaction product, comprising reacting an optically active organic compound having an amino group with an amino group leaving agent containing a compound (a) represented by the following formula (a), and further reacting the compound with a nucleophile: １ -X １ -Rf-X ２ -Y２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0024]

[17] The optically active organic compound is represented by the following formula (b ＊ The method for producing an optically active reaction product according to

[16] , The above formula (b ＊ ) Medium, R １ and R ２ are not the same and each independently represents a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ and R ２ may be bonded to each other to form a ring.

[0025]

[18] The method for producing an optically active reaction product according to

[16] or

[17] , wherein the nucleophilic agent is used to substitute the amino group that has reacted with the amino group leaving group agent with a chemical species, and the chemical species comprises at least one chemical species selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, and a substituted or unsubstituted hydrocarbon group.

[0026]

[19] The optically active reaction product is represented by the following formula (d ＊The method for producing the optically active reaction product according to any one of

[16] to

[18] , The above formula (d ＊ ) Medium, R １ and R ２ are not the same and each independently represents a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ and R ２ may be bonded to each other to form a ring; Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

[0027] According to the present invention, it is possible to provide an amino leaving agent for efficiently producing a reaction product by reacting an organic compound having an amino group with an amino leaving agent and then reacting the resulting compound with a nucleophile, a method for producing a reaction product, a reaction precursor, a method for producing a reaction precursor, and a method for producing an optically active reaction product.

[0028] In this specification and claims, "aliphatic" is a relative concept to aromatic, and is defined as meaning a group, compound, etc. that does not have aromaticity. "Alkyl group" includes linear, branched, and cyclic monovalent saturated hydrocarbon groups, unless otherwise specified. The same applies to alkyl groups in alkoxy groups. "Alkylene group" includes linear, branched, and cyclic divalent saturated hydrocarbon groups, unless otherwise specified.

[0029] Unless otherwise specified, the term "alkenylene group" encompasses straight-chain, branched-chain, and cyclic divalent unsaturated hydrocarbon groups. Unless otherwise specified, the term "aryl group" is defined as a monovalent group obtained by removing one hydrogen atom from an aromatic hydrocarbon ring. The same applies to the aryl group in a phenoxy group. Unless otherwise specified, the term "heteroaryl group" is defined as a monovalent group obtained by removing one hydrogen atom from an aromatic heterocycle. The same applies to the heteroaryl group in a heteroaryloxy group.

[0030] Examples of "halogen atoms" include fluorine atoms, chlorine atoms, bromine atoms, and iodine atoms. Examples of "polar groups" include carboxy groups, hydroxyl groups, amino groups, and sulfo groups (-SO ３ When describing "substituted or unsubstituted", it refers to the case where a hydrogen atom (-H) is substituted with a monovalent substituent, or the case where a methylene group (-CH ２ This includes both cases where a methine group (>CH- or ═CH-) is replaced with a divalent substituent. Examples of "monovalent substituents" include alkyl groups, alkoxy groups, halogen atoms, halogenated alkyl groups, hydroxy groups, carboxy groups, amino groups, and nitro groups.

[0031] The alkyl group as a substituent is preferably an alkyl group having 1 to 5 carbon atoms, and most preferably a methyl group, an ethyl group, a propyl group, an n-butyl group, or a tert-butyl group. The alkoxy group as a substituent is preferably an alkoxy group having 1 to 5 carbon atoms, and more preferably a methoxy group, an ethoxy group, an n-propoxy group, an iso-propoxy group, an n-butoxy group, or a tert-butoxy group, and most preferably a methoxy group or an ethoxy group.

[0032] The halogen atom as a substituent is preferably a fluorine atom or an iodine atom. Examples of the halogenated alkyl group as a substituent include alkyl groups having 1 to 5 carbon atoms, such as methyl, ethyl, propyl, n-butyl, and tert-butyl groups, in which some or all of the hydrogen atoms have been substituted with the halogen atoms.

[0033] The "divalent substituent" includes -O-, -C(=O)-O-, -O-C(=O)-, -C(=O)-, -O-C(=O)-O-, -C(=O)-NH-, -C(=O)-NH-C(=O)-, -N=, -NH-, -NH-C(=NH)- (H may be substituted with a substituent such as a hydrocarbon group, an acyl group or an alkoxyalkyl group), -S-, -S(=O) ２ -, -S(=O) ２ -O-, general formula -Y ２１ -O-Y ２２ -, -Y ２１ -O-, -Y ２１ -C(=O)-O-, -C(=O)-O-Y ２１ -, -[Y ２１ -C(=O)-O] ｍ” -Y ２２ -, -Y ２１ -OC(=O)-Y ２２ -or-Y ２１ -S(=O) ２ -O-Y ２２ -, wherein Y ２１ and Y ２２ are each independently a substituted or unsubstituted divalent hydrocarbon group, O is an oxygen atom, and m″ is an integer of 0 to 3.

[0034] <Amino Group Leaving Group Producing Agent> A first aspect of the present invention is an amino group leaving group producing agent comprising a compound (a) represented by the following formula (a), which is used to produce a reaction product by reacting an organic compound having an amino group with the amino group leaving group producing agent and then reacting the resulting compound with a nucleophile: Y １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0035] Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom. Substituted or unsubstituted divalent hydrocarbon group: The substituted or unsubstituted divalent hydrocarbon group in Rf may be an aliphatic hydrocarbon group or an aromatic hydrocarbon group. In Rf, at least one hydrogen atom in the substituted or unsubstituted divalent hydrocarbon group is substituted with a fluorine atom.

[0036] Aliphatic hydrocarbon group: An aliphatic hydrocarbon group refers to a hydrocarbon group that does not have aromaticity. The aliphatic hydrocarbon group may be saturated or unsaturated (for example, an alkenylene group, an alkynylene group, etc.). Examples of the aliphatic hydrocarbon group include a chain aliphatic hydrocarbon group and an aliphatic hydrocarbon group containing a ring in its structure. The chain aliphatic hydrocarbon group may be a straight-chain aliphatic hydrocarbon group or a branched-chain aliphatic hydrocarbon group.

[0037] ...Straight-chain or branched-chain aliphatic hydrocarbon group The straight-chain aliphatic hydrocarbon group preferably has 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, even more preferably 1 to 4 carbon atoms, and most preferably 1 to 3 carbon atoms. As the straight-chain aliphatic hydrocarbon group, a straight-chain alkylene group is preferred, and specifically, a methylene group [—CH ２ -], ethylene group [-(CH ２ ) ２ -], trimethylene group [-(CH ２ ) ３ -], tetramethylene group [-(CH ２ ) ４ -], pentamethylene group [-(CH ２ ) ５The branched chain aliphatic hydrocarbon group preferably has 2 to 10 carbon atoms, more preferably 3 to 6 carbon atoms, even more preferably 3 or 4 carbon atoms, and most preferably 3 carbon atoms. As the branched chain aliphatic hydrocarbon group, a branched chain alkylene group is preferred, and specifically, -CH(CH ３ ) -, -CH(CH ２ CH ３ ) -, -C(CH ３ ) ２ -, -C(CH ３ ) (CH ２ CH ３ ) -, -C(CH ３ ) (CH ２ CH ２ CH ３ ) -, -C(CH ２ CH ３ ) ２ alkylmethylene groups such as -; -CH(CH ３ ) CH ２ -, -CH(CH ３ ) CH(CH ３ ) -, -C(CH ３ ) ２ CH ２ -, -CH(CH ２ CH ３ ) CH ２ -, -C(CH ２ CH ３ ) ２ -CH ２ alkylethylene groups such as -; -CH(CH ３ ) CH ２ CH ２ -, -CH ２ CH (CH ３ ) CH ２ alkyltrimethylene groups such as -; -CH(CH ３ ) CH ２ CH ２ CH ２ -, -CH ２ CH (CH ３ ) CH ２ CH ２ The alkyl group in the alkylalkylene group is preferably a linear alkyl group having 1 to 5 carbon atoms.

[0038] The linear or branched aliphatic hydrocarbon group may or may not have a substituent.

[0039] ...Aliphatic hydrocarbon groups containing a ring in their structure Examples of aliphatic hydrocarbon groups containing a ring in their structure include cyclic aliphatic hydrocarbon groups (groups in which two hydrogen atoms have been removed from an aliphatic hydrocarbon ring) which may contain a substituent containing a heteroatom in the ring structure, groups in which the cyclic aliphatic hydrocarbon group is bonded to the end of a straight-chain or branched-chain aliphatic hydrocarbon group, and groups in which the cyclic aliphatic hydrocarbon group is interposed in the middle of a straight-chain or branched-chain aliphatic hydrocarbon group. Examples of the straight-chain or branched-chain aliphatic hydrocarbon group include the same as those described above. The cyclic aliphatic hydrocarbon group preferably has 3 to 20 carbon atoms, and more preferably 3 to 12 carbon atoms.

[0040] The cyclic aliphatic hydrocarbon group may be a polycyclic group or a monocyclic group. The monocyclic alicyclic hydrocarbon group is preferably a group in which two hydrogen atoms have been removed from a monocycloalkane. The monocycloalkane preferably has 3 to 6 carbon atoms, and specific examples thereof include cyclopropane, cyclopentane, and cyclohexane. The polycyclic alicyclic hydrocarbon group is preferably a group in which two hydrogen atoms have been removed from a polycycloalkane, and specific examples thereof include adamantane, norbornane, isobornane, tricyclodecane, and tetracyclododecane.

[0041] The cyclic aliphatic hydrocarbon group may or may not have a substituent. Examples of the substituent include an alkyl group, an alkoxy group, a halogen atom, a halogenated alkyl group, a hydroxy group, and a carbonyl group. Some of the carbon atoms constituting the ring structure of the cyclic aliphatic hydrocarbon group may be substituted with a substituent containing a heteroatom. Examples of the substituent containing a heteroatom include -O-, -C(=O)-O-, -S-, and -S(=O) ２ -, -S(=O) ２ —O— is preferred.

[0042] Aromatic hydrocarbon group: The aromatic hydrocarbon group is a hydrocarbon group having at least one aromatic ring. This aromatic ring is not particularly limited as long as it is a cyclic conjugated system having 4n+2 π electrons, and may be monocyclic or polycyclic. The aromatic ring preferably has 5 to 30 carbon atoms, more preferably 5 to 20 carbon atoms, even more preferably 6 to 15 carbon atoms, and particularly preferably 6 to 12 carbon atoms. However, this number of carbon atoms does not include the number of carbon atoms in the substituent.

[0043] Specific examples of the aromatic ring include aromatic hydrocarbon rings such as benzene, naphthalene, anthracene, and phenanthrene; and aromatic heterocycles in which a portion of the carbon atoms constituting the aromatic hydrocarbon ring is substituted with a heteroatom. Examples of the heteroatom in the aromatic heterocycle include an oxygen atom, a sulfur atom, and a nitrogen atom. Specific examples of the aromatic heterocycle include a pyridine ring and a thiophene ring.

[0044] Specific examples of the aromatic hydrocarbon group include groups in which two hydrogen atoms have been removed from the aromatic hydrocarbon ring or aromatic heterocycle (arylene groups or heteroarylene groups); groups in which two hydrogen atoms have been removed from an aromatic compound containing two or more aromatic rings (e.g., biphenyl, fluorene, etc.); and groups in which one hydrogen atom of a group in which one hydrogen atom has been removed from the aromatic hydrocarbon ring or aromatic heterocycle (aryl group or heteroaryl group) has been substituted with an alkylene group (e.g., groups in which one hydrogen atom has been further removed from the aryl group in an arylalkyl group such as a benzyl group, phenethyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-naphthylethyl group, or 2-naphthylethyl group). The alkylene group bonded to the aryl group or heteroaryl group preferably has 1 to 4 carbon atoms, more preferably 1 or 2 carbon atoms, and particularly preferably 1 carbon atom.

[0045] The aromatic hydrocarbon group may have a hydrogen atom substituted with a substituent. For example, a hydrogen atom bonded to an aromatic ring in the aromatic hydrocarbon group may be substituted with a substituent. Examples of the substituent include an alkyl group, an alkoxy group, a halogen atom, a halogenated alkyl group, and a hydroxy group.

[0046] The divalent hydrocarbon group for Rf is preferably a substituted or unsubstituted linear, branched, or cyclic aliphatic hydrocarbon group; a substituted or unsubstituted aromatic hydrocarbon group; or a combination of two or more thereof; and more preferably a substituted or unsubstituted linear, branched, or cyclic aliphatic hydrocarbon group; a substituted or unsubstituted aromatic hydrocarbon group; or a combination of two or more thereof.

[0047] The number of carbon atoms in the divalent hydrocarbon group in Rf is preferably 2 to 10, more preferably 2 to 8, still more preferably 2 to 6, and particularly preferably 2 to 4. The number of fluorine atoms in Rf is preferably 1 to 10, more preferably 2 to 8, still more preferably 3 to 10, and particularly preferably 3 to 8. Specifically, a difluoromethylene group [—CF ２ -], perfluoroethylene group [-(CF ２ ) ２ -], perfluorotrimethylene group [-(CF ２ ) ３ -], perfluorotetramethylene group [-(CF ２ ) ４ -], perfluoropentamethylene group [-(CF ２ ) ５ -], a perfluorophenyl group, etc. are preferred.

[0048] X １ and X ２ are each independently a carbonyl group or a sulfonyl group. １ and X ２ At least one of the groups is preferably a sulfonyl group, and more preferably both are sulfonyl groups.

[0049] Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0050] ・Halogen atom Y １and Y ２ Examples of the halogen atom in include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and among these, a fluorine atom is preferred.

[0051] - A substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, and a substituted or unsubstituted arylsulfonyloxy group Y １ and Y ２ In the substituted or unsubstituted alkylcarbonyloxy group, substituted or unsubstituted arylcarbonyloxy group, substituted or unsubstituted alkylsulfonyloxy group, and substituted or unsubstituted arylsulfonyloxy group in the above, examples of the alkyl group and the aryl group include the same as those described above for the alkyl group and the aryl group.

[0052] The amino leaving group agent may contain optional components such as a solvent, a compound containing a transition metal, a compound containing a ligand, and an organic catalyst in addition to the compound (a).

[0053] The organic compound has at least one amino group. The number of amino groups in the organic compound is not limited to 1, and is preferably 1 to 5, and more preferably 1 to 3.

[0054] The organic compound is preferably represented by the following formula (b):

[0055]

[0056] In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0057] Polar Group In formula (b), examples of the polar group include a carboxy group, a hydroxyl group, an amino group, and a sulfo group (-SO３ H) and the like.

[0058] Saturated Hydrocarbon Group In formula (b), examples of the saturated hydrocarbon group include linear or branched saturated hydrocarbon groups having 1 to 10 carbon atoms and cyclic saturated hydrocarbon groups having 3 to 10 carbon atoms. Specific examples of linear or branched saturated hydrocarbon groups having 1 to 10 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, 2-ethylhexyl, nonyl, and decyl groups. Specific examples of cyclic saturated hydrocarbon groups having 3 to 10 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl groups. R １ , R ２ and R ３ Examples of the ring formed by bonding at least two of the above to each other include a saturated cyclic hydrocarbon group having 3 to 10 carbon atoms and an unsaturated cyclic hydrocarbon group having 3 to 10 carbon atoms. Specific examples of the saturated cyclic hydrocarbon group having 3 to 10 carbon atoms include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, and a cyclodecyl group. Specific examples of the unsaturated cyclic hydrocarbon group having 3 to 10 carbon atoms include a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group, a cyclononenyl group, and a cyclodecenyl group.

[0059] Unsaturated Hydrocarbon Group In formula (b), examples of the unsaturated hydrocarbon group include linear or branched unsaturated hydrocarbon groups having 2 to 10 carbon atoms and cyclic unsaturated hydrocarbon groups having 3 to 10 carbon atoms. Specific examples of the linear or branched unsaturated hydrocarbon group having 2 to 10 carbon atoms include alkenyl groups such as vinyl, propenyl, butenyl, pentenyl, and hexenyl. Specific examples of the cyclic unsaturated hydrocarbon group having 3 to 10 carbon atoms include cycloalkenyl groups such as cyclopropenyl, cyclobutenyl, cyclopentenyl, and cyclohexenyl.

[0060] Aromatic Hydrocarbon Group In formula (b), examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having 6 to 10 carbon atoms, such as a phenyl group, a methylphenyl group, an ethylphenyl group, a hydroxyphenyl group, a chlorophenyl group, a nitrophenyl group, and a naphthyl group.

[0061] R １ , R ２ and R ３ are each independently preferably a hydrogen atom, a carboxy group, a substituted or unsubstituted linear or branched saturated hydrocarbon group having 1 to 10 carbon atoms, a substituted or unsubstituted cyclic saturated hydrocarbon group having 3 to 10 carbon atoms, a substituted or unsubstituted linear or branched unsaturated hydrocarbon group having 2 to 10 carbon atoms, a substituted or unsubstituted cyclic unsaturated hydrocarbon group having 3 to 10 carbon atoms, or a substituted or unsubstituted aromatic hydrocarbon group having 6 to 10 carbon atoms; and are more preferably a hydrogen atom, a carboxy group, a substituted or unsubstituted linear or branched saturated hydrocarbon group having 1 to 10 carbon atoms, a substituted or unsubstituted cyclic saturated hydrocarbon group having 3 to 10 carbon atoms, or a substituted or unsubstituted aromatic hydrocarbon group having 6 to 10 carbon atoms.

[0062] R １ , R ２ and R ３ The ring formed by bonding at least two of the above to each other is preferably a substituted or unsubstituted saturated cyclic hydrocarbon group having 3 to 10 carbon atoms, a substituted or unsubstituted unsaturated cyclic hydrocarbon group having 3 to 10 carbon atoms, or a substituted or unsubstituted aromatic hydrocarbon group having 6 to 10 carbon atoms, and more preferably a substituted or unsubstituted saturated cyclic hydrocarbon group having 3 to 10 carbon atoms, or a substituted or unsubstituted aromatic hydrocarbon group having 6 to 10 carbon atoms.

[0063] R １ , R ２ and R ３ In the formula (I), the monovalent substituent that substitutes the hydrogen atom (—H) is preferably an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a carboxy group, or a nitro group, and more preferably an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a halogen atom, or a nitro group.

[0064] R １ , R ２ and R ３ In the formula, a methylene group (-CH ２ Examples of the divalent substituent that replaces a methine group (>CH- or =CH-) include -O-, -C(=O)-O-, -O-C(=O)-, -C(=O)-, -O-C(=O)-O-, -C(=O)-NH-, -C(=O)-NH-C(=O)-, -N=, -NH-, -NH-C(=NH)- (H may be substituted by a substituent such as a hydrocarbon group, an acyl group or an alkoxyalkyl group), -S-, -S(=O) ２ -, -S(=O) ２ -O-, general formula -Y ２１ -O-Y ２２ -, -Y ２１ -O-, -Y ２１ -C(=O)-O-, -C(=O)-O-Y ２１ -, -[Y ２１ -C(=O)-O] ｍ” -Y ２２ -, -Y ２１ -OC(=O)-Y ２２ -, wherein Y ２１ and Y ２２ are each independently a substituted or unsubstituted divalent hydrocarbon group having 2 to 10 carbon atoms, O is an oxygen atom, and m″ is an integer of 0 to 3.

[0065] The nucleophilic agent is used to substitute the amino group that has reacted with the amino group leaving agent with a chemical species that contains at least one selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, and a substituted or unsubstituted hydrocarbon group.

[0066] Examples of the nucleophilic agent having a hydrogen atom include sodium hydride, sodium borohydride, and lithium aluminum hydride.

[0067] Examples of the nucleophilic agent having a hydroxyl group include water, sodium hydroxide, and potassium hydroxide.

[0068] Examples of nucleophiles having a halogen atom include fluorinating agents such as hydrogen fluoride, sodium fluoride, potassium fluoride, cesium fluoride, silver fluoride, triethylamine trihydrogen fluoride, hydrogen fluoride pyridine, tetramethylammonium fluoride, tetrabutylammonium fluoride (TBAF), and tetrabutylammonium difluorotriphenylsilicate (TBAT); sodium bromide; tetrabutylammonium chloride; sodium iodide; etc. Among these, tetrabutylammonium difluorotriphenylsilicate (TBAT) is preferred.

[0069] Examples of nucleophiles having a substituted or unsubstituted alkoxy group include substituted or unsubstituted alcohols having 1 to 10 carbon atoms and substituted or unsubstituted metal alkoxides having 1 to 10 carbon atoms. Examples of unsubstituted alcohols having 1 to 10 carbon atoms include methanol, ethanol, and propanol. Examples of substituted alcohols having 1 to 10 carbon atoms are preferably alcohols having 1 to 10 carbon atoms substituted with at least one fluorine atom, and more preferably alcohols having 1 to 10 carbon atoms substituted with 1 to 11 fluorine atoms. Specific examples of substituted alcohols having 1 to 10 carbon atoms include trifluoromethanol, trifluoroethanol, pentafluoropropanol, tetrafluoropropanol, perfluoroethanol, perfluoropropanol, and 1H,1H,2H,2H-tridecafluoro-1-n-octanol. Examples of unsubstituted metal alkoxides having 1 to 10 carbon atoms include sodium methoxide, sodium ethoxide, and sodium propoxide.

[0070] Examples of the nucleophilic agent having a substituted or unsubstituted aryloxy group include phenol and sodium phenoxide.

[0071] Examples of nucleophiles having an azide group include trimethylsilyl azide and sodium azide.

[0072] Examples of nucleophiles having a substituted or unsubstituted amino group include monoalkylamines having one alkyl group having 1 to 10 carbon atoms, dialkylamines having two alkyl groups having 1 to 10 carbon atoms, and trialkylamines having three alkyl groups having 1 to 10 carbon atoms. Specific examples of monoalkylamines having one alkyl group having 1 to 10 carbon atoms include methylamine, ethylamine, and propylamine. Specific examples of dialkylamines having two alkyl groups having 1 to 10 carbon atoms include dimethylamine, methylethylamine, diethylamine, and dipropylamine. Specific examples of trialkylamines having three alkyl groups having 1 to 10 carbon atoms include trimethylamine, N,N-dimethylethylamine, N,N-diethylmethylamine, triethylamine, and tripropylamine.

[0073] Examples of nucleophiles having a substituted or unsubstituted aromatic heterocyclic group include pyrrole, imidazole, 1-methylimidazole, pyridine, etc. Examples of nucleophiles having a substituted or unsubstituted alkylthio group include methanethiol, ethanethiol, propanethiol, etc.

[0074] Examples of nucleophiles having a substituted or unsubstituted arylthio group include thiophenol, etc. Examples of nucleophiles having a cyano group include trimethylsilyl cyanide, etc.

[0075] Examples of the nucleophilic agent having a substituted or unsubstituted phosphino group include trialkylphosphines such as trimethylphosphine; and triarylphosphines such as triphenylphosphine.

[0076] Examples of nucleophiles having a substituted or unsubstituted amide group include alkylamides such as acetamide and trifluoroacetamide; arylamides such as benzamide; and compounds having an imide such as phthalimide.

[0077] Examples of nucleophiles having a substituted or unsubstituted sulfonamide group include alkylsulfonamides such as trifluoromethanesulfonamide and potassium trifluoromethanesulfonamide; arylsulfonamides such as benzenesulfonamide; alkylsulfonimides such as potassium bis(trifluoromethanesulfonyl)imide; and arylsulfonimides such as diphenylsulfonimide.

[0078] Examples of nucleophiles having a substituted or unsubstituted hydrocarbon group include Grignard reagents such as alkyl Grignard reagents and aryl Grignard reagents; malonic acid esters such as dimethyl malonate and diethyl malonate; and acetoacetic acid esters such as methyl acetoacetate and ethyl acetoacetate.

[0079] The reaction product is preferably represented by the following formula (d):

[0080]

[0081] In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; and Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

[0082] In formula (d), R １ , R ２ and R ３In formula (d), Nu can be the same as those described for the chemical species possessed by the nucleophile.

[0083] According to the amino group leaving group generating agent of the first aspect of the present invention, a compound having two reactive sites in the same molecule is used as the amino group leaving group generating agent to directly replace the amino group constituting a primary alkylamine compound with a fluorine group or the like, which could not be converted using conventional nucleophiles. This makes it possible to efficiently produce fluorinated alkyl compounds and the like. This makes it possible to synthesize reaction products such as fluorine compounds, which have been difficult to synthesize in the past, and to simplify the synthesis process. Furthermore, by using primary alkylamines, which are abundantly present as natural products, as synthetic raw materials, it becomes possible to efficiently produce fluorinated alkyl compounds and the like at low cost.

[0084] <Method for Producing Reaction Product> A second aspect of the present invention is a method for producing a reaction product, which comprises reacting an amino group-containing organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a), and further reacting the organic compound with a nucleophile: Y １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0085] In formula (d), Y １ , X １ , Rf, X ２ , and Y ２ Examples of the formula (a) include the same as those described above for the formula (a) in the first embodiment of the present invention.

[0086] Examples of the organic compound having an amino group include the same compounds as those described in the first aspect of the present invention. Examples of the nucleophilic agent include the same compounds as those described in the first aspect of the present invention.

[0087] The method for producing a reaction product in a second aspect of the present invention includes reacting an organic compound having an amino group with an amino leaving group agent containing a compound (a) represented by the following formula (a) (hereinafter also referred to as the first reaction step), and further reacting the organic compound with a nucleophile (hereinafter also referred to as the second reaction step). This may be a multi-step reaction in which the product obtained after the first reaction step is isolated and then the second reaction step is carried out, or it may be a one-pot synthesis in which the first reaction step and the second reaction step proceed continuously. One-pot synthesis is preferred because it allows for efficient production of the reaction product.

[0088] In the first reaction step and the second reaction step, a basic substance, a solvent, etc. may be used.

[0089] Specific examples of basic substances include trimethylamine, triethylamine, diisopropylamine, tripropylamine, pyridine, 4-dimethylaminopyridine (DMAP), diazachloundecene (DBU), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), diazabicyclononene (DBN), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-enepyridine (MTBD), tert-butylimino-tris(dimethylamino)phosphorane, tert-butylimino-tri(pyrrolidino)phosphorane (BTPP), 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), etc. Of these, diazachloundecene (DBU) is particularly preferred.

[0090] The amount of the basic substance used relative to the organic compound having an amino group is determined by the amount of reactive amino group (NH ２ The amount of the basic substance used is preferably in the range of 0.5 moles or more and 10 moles or less, and more preferably in the range of 1.5 moles or more and 3.0 moles or less, relative to 1 mole of the reactive amino group (NH ２If the amount of the basic substance used is 0.5 moles or more per mole of the reactive amino group (NH − ), the amount of the reaction product produced is less likely to be less than the reaction equivalent. ２ -) If the amount is 10 moles or less relative to 1 mole of base, the reaction product is less likely to be decomposed by an excess amount of base.

[0091] The amount of the nucleophilic agent used relative to the organic compound having an amino group is determined by the amount of reactive amino group (NH ２ The amount of the nucleophilic agent used is preferably in the range of 1 mole or more and 10 moles or less, and more preferably in the range of 1.3 moles or more and 3.0 moles or less, relative to 1.0 mole of the reactive amino group (NH ２ If the amount of the nucleophilic agent is 1.0 mole or more per mole of the reactive amino group (NH − ), the amount of the nucleophilic agent used can be minimized, which makes it easier to reduce production costs. ２ -) If the amount is 10 moles or less relative to 1 mole, the reaction time can be easily shortened, and the amount of nucleophilic agent used can be reduced, making it easier to keep production costs down.

[0092] The solvent is preferably an aprotic solvent. Specific examples of the aprotic solvent include acetonitrile, propionitrile, dimethylformamide, dimethylacetamide, methylformamide, N-methylpyrrolidone, diethyl ether, diisopropyl ether, tert-butyl methyl ether, cyclopentyl methyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 1,3-dioxane, 1,4-dioxane, diglyme, triglyme, dimethyl sulfoxide, sulfolane, pentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylene, and ethylbenzene. Of these, toluene is particularly preferred as the solvent. Furthermore, a mixture of multiple solvents can also be used.

[0093] The reaction temperatures in both the first and second reaction steps are preferably in the range of 0°C or higher and the boiling point of the solvent or lower, more preferably in the range of 100 to 200°C, and even more preferably in the range of 130 to 150°C. If the reaction temperature is 0°C or higher, the reaction proceeds easily. Furthermore, the first and second reaction steps are preferably carried out under conditions in which the solvent is refluxed.

[0094] The reaction time for the first and second reaction steps is preferably in the range of 1 hour to 3 hours, but even if the reaction time is about 30 minutes, 50% or more of the entire reaction has progressed, so depending on the temperature conditions, the reaction temperature may be less than 1 hour.

[0095] If the reaction is slow, the reaction can be carried out in an autoclave or under microwave irradiation. The reaction temperature is preferably in the range of 100 to 200°C, more preferably in the range of 130 to 150°C. The reaction time is preferably in the range of 10 minutes to 3 hours, more preferably in the range of 30 minutes to 1 hour.

[0096] According to the method for producing a reaction product in the second aspect of the present invention, a compound having two reactive sites in the same molecule is used as a deaminating agent to directly substitute fluorine groups or the like for the amino groups constituting a primary alkylamine compound, which could not be converted using conventional nucleophiles. This makes it possible to efficiently produce fluorinated alkyl compounds and the like. This makes it possible to synthesize reaction products such as fluorine compounds, which have been difficult to synthesize in the past, and to simplify the synthesis process. Furthermore, by using primary alkylamines, which are abundantly present as natural products, as synthetic raw materials, it becomes possible to efficiently produce fluorinated alkyl compounds and the like at low cost.

[0097] <Reaction Precursor> A third aspect of the present invention is a reaction precursor for obtaining a reaction product by reacting with a nucleophile, the reaction precursor comprising a compound (e) represented by the following formula (e) or a compound (f) represented by the following formula (f):

[0098]

[0099]

[0100] In the above formulas (e) and (f), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y ２is a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group; M １ is a hydrogen atom or has a counter ion; R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0101] In formulas (e) and (f), X １ , Rf, X ２ , and Y ２ In the first embodiment of the present invention, R is the same as that described for formula (a). １ , R ２ and R ３ The formula (b) may be the same as those described for the formula (b) in the first embodiment of the present invention.

[0102] The nucleophilic agent may be the same as that described in the first aspect of the present invention. The reaction product may be the same as that described in the first aspect of the present invention.

[0103] In formulas (e) and (f), the tertiary amino group bonded to the carbonyl group or sulfonyl group is substituted with the chemical species Nu contained in the nucleophile by reacting with the nucleophile, thereby obtaining a reaction product.

[0104] The reaction precursor may contain optional components such as a solvent, a basic substance, a nucleophilic agent, a compound containing a transition metal, a compound containing a ligand, and an organic catalyst, in addition to the compound (e) or (f).

[0105] According to the reaction precursor in the third aspect of the present invention, a desired reaction product can be obtained in just one step by reacting it with various nucleophiles, and therefore a synthetic intermediate useful in the fields of medicine, agricultural chemicals, electronic materials, functional materials, etc. can be provided.

[0106] <Method for producing a reaction precursor> A fourth aspect of the present invention is a method for producing a reaction precursor containing a compound (e) represented by the following formula (e) or a compound (f) represented by the following formula (f) for obtaining a reaction product by reacting with a nucleophilic agent, the method comprising reacting an amino group-containing organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a): １ -X １ -Rf-X ２ -Y ２ ...(a)

[0107] In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0108]

[0109]

[0110] In the above formulas (e) and (f), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y ２is a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group; M １ is a hydrogen atom or a counter ion; R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

[0111] In formula (a), Y １ , X １ , Rf, X ２ , and Y ２ In the first embodiment of the present invention, X may be the same as that described above for formula (a). １ , Rf, X ２ , and Y ２ In the first embodiment of the present invention, R is the same as that described for formula (a). １ , R ２ and R ３ The formula (b) may be the same as those described for the formula (b) in the first embodiment of the present invention.

[0112] The nucleophilic agent may be the same as that described in the first aspect of the present invention. The reaction product may be the same as that described in the first aspect of the present invention.

[0113] A method for producing a reaction precursor in a fourth aspect of the present invention includes reacting an organic compound having an amino group with an amino leaving group agent containing a compound (a) represented by the following formula (a) (hereinafter also referred to as the first reaction step). Here, the first reaction step may include reacting an organic compound having an amino group with an amino leaving group agent containing a compound (a) represented by the following formula (a) (hereinafter also referred to as the 1a reaction step). The 1a reaction step can synthesize a compound (e) represented by formula (e). The 1a reaction step may further include obtaining a compound (f) represented by formula (f) from the compound (e) represented by formula (e) (hereinafter also referred to as the 1b reaction step). The 1b reaction step can synthesize a compound (f) represented by formula (f). A one-pot synthesis in which the 1a reaction step and the 1b reaction step proceed continuously may be performed. The one-pot synthesis is preferred because it allows the reaction product to be produced efficiently.

[0114] When compound (e) or compound (f) is used in the production of a reaction product, a multi-step reaction may be performed in which reaction step 1a is performed to synthesize compound (e) and isolate it, reaction step 1b is performed to synthesize compound (f), and reaction step 2 is performed to synthesize the reaction product, or a one-pot synthesis may be performed in which reaction steps 1a and 2 are performed continuously. One-pot synthesis is preferred because it allows the reaction product to be produced efficiently. A multi-step reaction may be performed in which one-pot synthesis is performed in which reaction steps 1a and 1b are performed continuously, and then the resulting product (compound (f)) is isolated and the second reaction step is performed, or a one-pot synthesis in which reaction steps 1b and 2 are performed continuously. One-pot synthesis is preferred because it allows the reaction product to be produced efficiently.

[0115] In the reaction step 1a and the reaction step 1b, a basic substance, a solvent, and the like can be used.

[0116] Examples of the basic substance and solvent include the same as those described in the second aspect of the present invention.

[0117] The amount of the basic substance used relative to the compound (e) is determined based on the amount of reactive amino group (NH ２ The amount of the basic substance used is preferably in the range of 0.5 moles or more and 10 moles or less, and more preferably in the range of 1.5 moles or more and 3.0 moles or less, relative to 1 mole of the reactive amino group (NH ２ If the amount of the basic substance used is 0.5 moles or more per mole of the reactive amino group (NH − ), the amount of the reaction product produced is less likely to be less than the reaction equivalent. ２ -) If the amount is 10 moles or less relative to 1 mole of base, the reaction product is less likely to be decomposed by an excess amount of base.

[0118] The amount of the basic substance used relative to the compound (f) is determined based on the amount of reactive amino group (NH ２ The amount of the basic substance used is preferably in the range of 0.5 moles or more and 10 moles or less, and more preferably in the range of 1.5 moles or more and 3.0 moles or less, relative to 1 mole of the reactive amino group (NH ２ If the amount of the basic substance used is 0.5 moles or more per mole of the reactive amino group (NH − ), the amount of the reaction product produced is less likely to be less than the reaction equivalent. ２ -) If the amount is 10 moles or less relative to 1 mole of base, the reaction product is less likely to be decomposed by an excess amount of base.

[0119] The amount of the nucleophilic agent used relative to the compound (e) is determined by the amount of the reactive amino group (NH ２ The amount of the nucleophilic agent used is preferably in the range of 1 mole or more and 10 moles or less, and more preferably in the range of 1.3 moles or more and 3.0 moles or less, relative to 1.0 mole of the reactive amino group (NH ２ If the amount of the nucleophilic agent is 1.0 mole or more per mole of the reactive amino group (NH − ), the amount of the nucleophilic agent used can be minimized, which makes it easier to reduce production costs. ２ -) If the amount is 10 moles or less relative to 1 mole, the reaction time can be easily shortened, and the amount of nucleophilic agent used can be reduced, making it easier to keep production costs down.

[0120] The amount of the nucleophilic agent used relative to the compound (f) is determined by the amount of the reactive amino group (NH ２The amount of the nucleophilic agent used is preferably in the range of 1 mole or more and 10 moles or less, and more preferably in the range of 1.3 moles or more and 3.0 moles or less, relative to 1.0 mole of the reactive amino group (NH ２ If the amount of the nucleophilic agent is 1.0 mole or more per mole of the reactive amino group (NH − ), the amount of the nucleophilic agent used can be minimized, which makes it easier to reduce production costs. ２ -) If the amount is 10 moles or less relative to 1 mole, the reaction time can be easily shortened, and the amount of nucleophilic agent used can be reduced, making it easier to keep production costs down.

[0121] The reaction temperatures of both reaction steps 1a and 1b are preferably in the range of 0°C or higher and the boiling point of the solvent or lower. If the reaction temperature is 0°C or higher, the reaction proceeds easily. Furthermore, reaction steps 1a and 1b are preferably reacted under conditions of refluxing the solvent. The reaction temperature of reaction step 1b is preferably higher than the reaction temperature of reaction step 1a. [Reaction temperature of reaction step 1b] - [Reaction temperature of reaction step 1a] is preferably in the range of higher than 0°C and the boiling point of the solvent or lower, more preferably in the range of 30°C or higher and 100°C or lower. If the difference in reaction temperatures is within the above range, decomposition of reaction intermediates and production of by-products can be easily suppressed, making it easier to improve the yield of the reaction product.

[0122] The reaction time of reaction step 1a and reaction step 1b is preferably in the range of 1 hour or more and 3 hours or less. The reaction time of reaction step 1b is preferably longer than the reaction time of reaction step 1a. [Reaction time of reaction step 1b] - [Reaction time of reaction step 1a] is preferably in the range of more than 0 hours and 3 hours or less, and more preferably in the range of 30 minutes or more and 1 hour or less. If the difference in reaction time is within the above range, decomposition of reaction intermediates and production of by-products can be easily suppressed, and the yield of the reaction product can be easily improved.

[0123] If the reaction is slow, the reaction can be carried out in an autoclave or under microwave irradiation. The reaction temperature is preferably in the range of 100 to 200°C, more preferably in the range of 130 to 150°C. The reaction time is preferably in the range of 10 minutes to 3 hours, more preferably in the range of 30 minutes to 1 hour.

[0124] According to the method for producing a reaction precursor in the fourth aspect of the present invention, it is possible to provide a reaction precursor that can be reacted with various nucleophiles to give a desired reaction product in just one step, and therefore it is possible to provide a synthetic intermediate that is useful in fields such as medicine, agricultural chemicals, electronic materials, and functional materials.

[0125] <Method for producing optically active reaction product> A fifth aspect of the present invention is a method for producing an optically active reaction product, which comprises reacting an optically active organic compound having an amino group with an amino leaving group-forming agent containing a compound (a) represented by the following formula (a), and further reacting the compound with a nucleophile: Y １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf represents a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ are each independently a carbonyl group or a sulfonyl group; Y １ and Y ２ are each independently a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

[0126] In the above formula (a), Y １ , X １ , Rf, X ２ , and Y ２ Examples of the formula (a) include the same as those described above for the formula (a) in the first embodiment of the present invention.

[0127] The optically active organic compound is a compound represented by the following formula (b ＊ ) is preferably represented by the formula:

[0128]

[0129] The above formula (b ＊ ) Medium, R １ and R ２are not the same and each independently represents a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ and R ２ may be bonded to each other to form a ring.

[0130] Formula (b ＊ ) Medium, R １ and R ２ The formula (b) may be the same as those described for the formula (b) in the first embodiment of the present invention.

[0131] Examples of the nucleophilic agent include the same as those described in the first embodiment of the present invention.

[0132] The optically active reaction product is represented by the following formula (d ＊ ) is preferably represented by the formula:

[0133]

[0134] The above formula (d ＊ ) Medium, R １ and R ２ are not the same and each independently represents a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ and R ２ may be bonded to each other to form a ring.

[0135] Formula (d ＊ ) Medium, R １ and R ２ The formula (b) may be the same as those described for the formula (b) in the first embodiment of the present invention.

[0136] According to the method for producing an optically active reaction product in the fifth aspect of the present invention, a compound having two reactive sites in the same molecule is used as a deaminating agent to directly substitute a fluorine group or the like for the amino group constituting an optically active primary alkylamine compound, which could not be converted using conventional nucleophiles. This makes it possible to efficiently produce optically active fluorinated alkyl compounds, etc. This makes it possible to synthesize reaction products such as optically active fluorine compounds, which have been difficult to synthesize in the past, and to simplify the synthesis process. Furthermore, by using optically active primary alkylamines, which are abundantly present as natural products such as amino acids, as synthetic raw materials for optically active reaction products that have been difficult to synthesize, it becomes possible to efficiently produce optically active fluorinated alkyl compounds at low cost.

[0137] Although the embodiments of the present invention have been described above, the technical scope of the present invention is not limited to the above embodiments, and various modifications can be made within the scope that does not deviate from the spirit of the present invention.

[0138] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. In the examples and comparative examples, unless otherwise specified, reaction products were synthesized under the same reaction conditions as in Example 1. The NMR apparatus used for analysis in the examples and comparative examples was an AVANCE 400 (manufactured by Bruker). １ H-NMR: 400 MHz, １９ F-NMR: 376 MHz). １ In H-NMR, tetramethylsilane was used as the reference value of 0 ppm, １９ In F-NMR, trichlorofluoromethane was used as the reference value at 0 ppm.

[0139] Example 1 An alkyl iodide compound represented by the following formula (d-1) was synthesized using a primary alkylamine represented by the following formula (b-1).

[0140]

[0141]

[0142] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and sodium iodide (374.7 mg, 2.5 mmol) were added to toluene (10 mL) and heated to 110°C. To this was slowly added diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol), and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=100 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d1-1) in a yield of 41%.

[0143] NMR analysis confirmed that the compound represented by the above formula (d1-1) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.31 to 7.26 (m, 2H), 7.21 to 7.18 (m, 3H), 4.14 to 4.09 (m, 1H), 2.88 to 2.66 (m, 2H), 2.20 to 2.11 (m, 1H), 1.95 (d, 3H), 1.92 to 1.84 (m, 1H).

[0144] Example 2 An alkyl bromide compound represented by the following formula (d-2) was synthesized using a primary alkylamine represented by the following formula (b-2).

[0145]

[0146]

[0147] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and sodium bromide (257.2 mg, 2.5 mmol) were added to toluene (10 mL) and heated to 110°C. To this was slowly added diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol), and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=100 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d-2) in a yield of 45%.

[0148] NMR analysis confirmed that the compound represented by the above formula (d-2) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.31 to 7.27 (m, 2H), 7.21 to 7.18 (m, 3H), 4.12 to 4.04 (m, 1H), 2.90 to 2.69 (m, 2H), 2.19 to 1.96 (m, 2H), 1.73 (d, 3H).

[0149] Example 3 An alkyl chloride compound represented by the following formula (d-3) was synthesized using a primary alkylamine represented by the following formula (b-3).

[0150]

[0151]

[0152] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and tetrabutylammonium chloride (694.7 mg, 2.5 mmol) were added to toluene (10 mL) and heated to 110°C. To this was slowly added diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol), and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=100 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d-3) in a yield of 75%.

[0153] NMR analysis confirmed that the compound represented by the above formula (d-3) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.31-7.27 (m, 2H), 7.21-7.18 (m, 3H), 4.03-3.95 (m, 1H), 2.89-2.71 (m, 2H), 2.08-1.95 (m, 2H), 1.53 (d, 3H).

[0154] Example 4 A fluorinated alkyl compound represented by the following formula (d-4) was synthesized using a primary alkylamine compound represented by the following formula (b-4).

[0155]

[0156]

[0157] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and tetrabutylammonium difluorotriphenylsilicate (TBAT) (135.0 mg, 0.25 mmol) were added to toluene (10 mL), and the mixture was heated to 110° C. Diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol) was slowly added thereto, and the mixture was stirred at 110° C. for 1 hour, and then quenched with 2 M aqueous hydrochloric acid solution (10 mL) to obtain a reaction solution.

[0158] Chloroform (10 mL) was added to the obtained reaction solution, and the layers were separated. The organic layer was then washed once with a 2 M aqueous hydrochloric acid solution (10 mL), and then washed twice with a saturated aqueous sodium carbonate solution (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was then distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=100 / 1), and the solvent was distilled off under reduced pressure, yielding the alkyl fluoride compound represented by formula (d-4) in a 53% yield.

[0159] NMR analysis confirmed that the compound was the alkyl fluoride compound represented by the above formula (d-4). １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.31-7.18 (m, 5H), 4.75-4.56 (m, 1H), 2.84-2.65 (m, 2H), 2.05-1.70 (m, 2H), 1.55-1.37 (m, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -174.04 to -174.36 (m, 1F).

[0160] Example 5 A primary alkylamine represented by the following formula (b-5) was used, and its amino group was converted to —OCH ２ CF ３ group to synthesize an alkyl ether compound represented by the following formula (d-5).

[0161]

[0162]

[0163] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and 2,2,2-trifluoroethanol (250.1 mg, 2.5 mmol) were added to toluene (10 mL) and heated to 110°C. To this was slowly added diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol), and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=10 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d-5) in a yield of 67%.

[0164] NMR analysis confirmed that the compound represented by the above formula (d-5) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.29-7.26 (m, 2H), 7.19-7.16 (m, 3H), 3.25-3.06 (m, 2H), 2.81-2.71 (m, 1H), 2.70-2.63 (m, 2H), 1.79-1.60 (m, 2H), 1.11 (d, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -72.15 to -72.20 (m, 3F).

[0165] Example 6 A primary alkylamine represented by the following formula (b-6) was used, and its amino group was converted to —OCH ２ CF ２ CF ３ group to synthesize an alkyl ether compound represented by the following formula (b-6).

[0166]

[0167]

[0168] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and 2,2,3,3,3-pentafluoro-1-propanol (187.6 mg, 1.25 mmol) were added to toluene (10 mL) and heated to 110°C. Diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol) was slowly added to the mixture, and the mixture was stirred for 1 hour and then quenched with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=10 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d-6) in a yield of 44%.

[0169] NMR analysis confirmed that the compound represented by the above formula (d-6) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.30-7.26 (m, 2H), 7.20-7.17 (m, 3H), 3.30-3.08 (m, 2H), 2.78-2.71 (m, 1H), 1.78-1.60 (m, 2H), 1.79-1.60 (m, 2H), 1.12 (d, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -83.80 to -83.83 (m, 3F), -121.81 to -121.89 (m, 2F).

[0170] Example 7 A primary alkylamine represented by the following formula (b-7) was used, and its amino group was converted to —OCH ２ CF ２ CF ２ By substituting with an H group, an alkyl ether compound represented by the following formula (d-7) was synthesized.

[0171]

[0172]

[0173] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and 2,2,3,3-tetrafluoro-1-propanol (165.1 mg, 1.25 mmol) were added to toluene (10 mL) and heated to 110°C. Diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol) was slowly added to the mixture, and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=10 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d-7) in a yield of 37%.

[0174] NMR analysis confirmed that the compound represented by the above formula (d-7) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.30-7.26 (m, 2H), 7.23-7.15 (m, 3H), 6.17-5.87 (m, 1H), 3.24-3.01 (m, 2H), 2.78-2.58 (m, 3H), 1.79-1.60 (m, 2H), 1.12 (d, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -122.72 to -123.01 (m, 2F), -139.57 to -139.88 (m, 2F).

[0175] Example 8 A primary alkylamine represented by the following formula (b-8) was used, and its amino group was converted to —OCH ２ CH ２ CF ２ CF２ CF ２ CF ２ CF ２ CF ３ group to synthesize an alkyl ether compound represented by the following formula (d-8).

[0176]

[0177]

[0178] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and 1H,1H,2H,2H-tridecafluoro-1-n-octanol (455.1 mg, 1.25 mmol) were added to toluene (10 mL) and heated to 110°C. To this was slowly added diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol), and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, and the mixture was separated. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was then distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate=10 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by formula (d-8) in a yield of 18%.

[0179] NMR analysis confirmed that the compound represented by the above formula (d-8) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.30-7.26 (m, 2H), 7.20-7.17 (m, 3H), 3.01-2.85 (m, 2H), 2.74-2.59 (m, 3H), 2.33-2.18 (m, 2H), 1.81-1.60 (m, 2H), 1.12 (d, 3H). １９ F-NMR (376MHz, CDCl ３) δ (ppm) = -80.74 to -80.79 (m, 3F), -113.55 to -113.64 (m, 2F), -121.89 (m, 2F), -122.86 (m, 2F), -123.66 (m, 2F), -126.07 to -126.17 (m, 2F).

[0180] Example 9 An alkyl azide compound represented by the following formula (d-9) was synthesized using a primary alkylamine represented by the following formula (b-9).

[0181]

[0182]

[0183] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (74.6 mg, 0.50 mmol), 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (316.2 mg, 1.0 mmol), and trimethylsilyl azide (144.0 mg, 1.25 mmol) were added to toluene (10 mL) and heated to 110°C. To this was slowly added diazabicycloundecene (DBU) (152.2 mg, 1.0 mmol), and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=10 / 1), and the solvent was distilled off under reduced pressure to obtain the compound represented by the above formula (d-9) in a yield of 64%.

[0184] NMR analysis confirmed that the compound represented by the above formula (d-9) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.31-7.27 (m, 2H), 7.23-7.17 (m, 3H), 3.45-3.40 (m, 1H), 2.78-2.62 (m, 2H), 1.85-1.75 (m, 2H), 1.28 (d, 3H).

[0185] Example 10 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-10), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-10).

[0186]

[0187]

[0188] Example 11 Using the primary alkylamine represented by formula (b-10) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-11) below was synthesized in a yield of 35%.

[0189]

[0190] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -219.94 to -220.32 (m, 1F).

[0191] Example 12 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-12), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-12).

[0192]

[0193]

[0194] Example 13 Using the primary alkylamine represented by formula (b-12) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-13) below was synthesized in a yield of 31%.

[0195]

[0196] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -215.02-215.39 (m, 1F).​​

[0197] Example 14 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-14), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-14).

[0198]

[0199]

[0200] Example 15 Using the primary alkylamine represented by formula (b-14) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-15) below was synthesized in a yield of 44%.

[0201]

[0202] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -215.87 to -216.24 (m, 1F).

[0203] Example 16 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-16), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-16).

[0204]

[0205]

[0206] Example 17 Using the primary alkylamine represented by formula (b-16) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-17) below was synthesized in a yield of 32%.

[0207]

[0208] １９ F-NMR (376MHz, CDCl ３ ​​) δ (ppm) = -215.88 to -216.25 (m, 1F).

[0209] Example 18 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-18), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-18).

[0210]

[0211]

[0212] Example 19 Using the primary alkylamine represented by formula (b-18) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-19) below was synthesized in a yield of 28%.

[0213]

[0214] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -173.62 to -174.09 (m, 1F).

[0215] Example 20 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-20), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-20).

[0216]

[0217]

[0218] Example 21 Using the primary alkylamine represented by formula (b-20) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-21) below was synthesized in a yield of 14%.

[0219]

[0220] １９ ​​F-NMR (376MHz, CDCl ３ ) δ (ppm) = -206.29 (t, 1F).

[0221] Example 22 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-22), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-22).

[0222]

[0223]

[0224] Example 23 Using the primary alkylamine represented by formula (b-22) above and tetrabutylammonium iodide as a nucleophile, an alkyl iodide compound represented by formula (d-23) below was synthesized in a yield of 19%.

[0225]

[0226] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.39 to 7.29 (m, 10H), 6.41 (s, 1H).

[0227] Example 24 Using the primary alkylamine represented by formula (b-22) above and tetrabutylammonium bromide as a nucleophile, an alkyl bromide compound represented by formula (d-24) below was synthesized in an 18% yield.

[0228]

[0229] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.44 to 7.20 (m, 10H), 6.27 (s, 1H).

[0230] Example 25 Using the primary alkylamine represented by formula (b-22) above and tetrabutylammonium chloride as a nucleophile, an alkyl chloride compound represented by formula (d-25) below was synthesized in a yield of 19%.

[0231] ​​

[0232] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.36 to 7.23 (m, 10H), 6.13 (s, 1H).

[0233] Example 26 Using the primary alkylamine represented by formula (b-22) above and 2,2,2-trifluoroethanol as a nucleophile, an alkyl ether compound represented by formula (d-26) below was synthesized in a yield of 65%.

[0234]

[0235] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.47 to 7.20 (m, 10H), 4.97 (s, 1H), 3.14 (q, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -71.21 (t, 3F).

[0236] Example 27 Using the primary alkylamine represented by formula (b-22) above and 2,2,3,3,3-pentafluoro-1-propanol as a nucleophile, an alkyl ether compound represented by formula (d-27) below was synthesized in a yield of 39%.

[0237]

[0238] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.45 to 7.19 (m, 10H), 4.94 (s, 1H), 3.22 to 3.14 (m, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -83.84 (m, 3F), -121.14 to -121.22 (m, 2F).

[0239] Example 28 Using the primary alkylamine represented by the above formula (b-22) and 2,2,3,3-tetrafluoro-1-propanol as a nucleophile, an alkyl ether compound represented by the following formula (d-28) was synthesized in a yield of 49%.​​​

[0240]

[0241] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.37-7.21 (m, 10H), 6.19-5.90 (m, 1H), 4.88 (s, 1H), 3.14-3.07 (m, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -122.09 to -122.20 (m, 2F), -138.71 to -138.87 (m, 2F).

[0242] Example 29 Using the primary alkylamine represented by formula (b-22) above and 1H,1H,2H,2H-tridecafluoro-1-n-octanol as a nucleophile, an alkyl ether compound represented by formula (d-29) below was synthesized in a yield of 15%.

[0243]

[0244] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.40 to 7.19 (m, 10H), 4.84 (s, 1H), 2.93 to 2.89 (m, 2H), 2.38 to 2.25 (m, 2H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -80.74 to -80.80 (m, 3F), -113.46 to -113.55 (m, 2F), -121.88 (m, 2 F), -122.87 (m, 2F), -123.60 to -123.63 (m, 2F), -126.07 to -126.16 (m, 2F).

[0245] [Example 30] Using the primary alkylamine represented by the above formula (b-22) and trimethylsilyl azide as a nucleophile, an alkyl azide compound represented by the following formula (d-30) was synthesized in a yield of 85%.

[0246]

[0247] １ H-NMR (400MHz, CDCl​​​３ ) δ (ppm) = 7.41 to 7.31 (m, 10H), 5.74 (s, 1H).

[0248] Example 31 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-31), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-31).

[0249]

[0250]

[0251] Example 32 Using the primary alkylamine represented by formula (b-31) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-32) below was synthesized in a yield of 12%.

[0252]

[0253] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -173.81 to -173.97 (m, 1F).

[0254] Example 33 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-33), and reacted with various nucleophiles, to obtain reaction products represented by the following formula (d-33).

[0255]

[0256]

[0257] Example 34 Using the primary alkylamine represented by formula (b-33) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-34) below was synthesized in a yield of 20%.

[0258]

[0259] ​​１９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -128.50 to -128.52 (m, 1F).

[0260] Example 35 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-35), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-35).

[0261]

[0262]

[0263] Example 36 Using the primary alkylamine represented by formula (b-35) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-36) below was synthesized in a yield of 12%.

[0264]

[0265] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -159.39 to -159.71 (m, 1F).

[0266] Example 37 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-37), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-37).

[0267]

[0268]

[0269] Example 38 Using the primary alkylamine represented by formula (b-37) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-38) below was synthesized in a yield of 41%.

[0270] ​

[0271] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -169.42 to -169.88 (m, 1F).

[0272] Example 39 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-39), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-39).

[0273]

[0274]

[0275] Example 40 Using the primary alkylamine represented by formula (b-39) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-40) below was synthesized. The yield was 2%.

[0276]

[0277] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -171.97 to -172.30 (m, 1F).

[0278] Example 41 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-41), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-41).

[0279]

[0280]

[0281] Example 42 Using the primary alkylamine represented by formula (b-41) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-42) below was synthesized in a yield of 51%. ​​

[0282]

[0283] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -163.25 to -163.57 (m, 1F).

[0284] Example 43 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-43), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-43).

[0285]

[0286]

[0287] Example 44 Using the primary alkylamine represented by formula (b-43) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-44) below was synthesized in a yield of 21%.

[0288]

[0289] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -158.27 to -158.91 (m, 1F).

[0290] Example 45 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-45), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-45).

[0291]

[0292]

[0293] ​​Example 46 Using the primary alkylamine represented by formula (b-45) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-46) below was synthesized in a yield of 23%.

[0294]

[0295] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -221.92 to -222.22 (m, 1F).

[0296] Example 47 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-47), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-47).

[0297]

[0298]

[0299] Example 48 Using the primary alkylamine represented by formula (b-47) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-48) below was synthesized in a yield of 32%.

[0300]

[0301] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -218.18 to -218.57 (m, 1F).

[0302] Example 49 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-49), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-49).

[0303]

[0304] ​​

[0305] Example 50 Using the primary alkylamine represented by formula (b-49) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-50) below was synthesized in a yield of 3%.

[0306]

[0307] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -189.97 to -190.24 (m, 1F).

[0308] Example 51 The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-51), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-51).

[0309]

[0310]

[0311] Example 52 Using the primary alkylamine represented by formula (b-51) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, an alkyl fluoride compound represented by formula (d-52) below was synthesized in a yield of 33%.

[0312]

[0313] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -181.99 to -182.33 (m, 1F).

[0314] Example 53 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-53), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-53).

[0315] ​​

[0316]

[0317] Example 54 Using the primary alkylamine represented by formula (b-53) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-54) below was synthesized in a yield of 16%.

[0318]

[0319] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -218.16 to -218.55 (m, 1F).

[0320] Example 55 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-55), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-55).

[0321]

[0322]

[0323] Example 56 Using the primary alkylamine represented by formula (b-55) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-56) below was synthesized in a yield of 21%.

[0324]

[0325] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -217.88 to -218.27 (m, 2F).

[0326] Example 57 A reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by formula (b-1) was changed to a primary alkylamine represented by the following formula (b-57), and reacted with various nucleophiles, to obtain a reaction product represented by the following formula (d-57).

[0327] ​​

[0328]

[0329] Example 58 Using the primary alkylamine represented by formula (b-57) above and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, a fluorinated alkyl compound represented by formula (d-58) below was synthesized in a yield of 36%.

[0330]

[0331] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -221.68 to -222.07 (m, 2F).

[0332] Example 59 A primary alkylamine represented by formula (b-1) was reacted with a compound represented by the following formula (b ＊ The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by the following formula (d ＊ -59) was obtained.

[0333]

[0334]

[0335] [Example 60] The above formula (b ＊ -59) and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, ＊ A fluorinated alkyl compound represented by the formula (I) was synthesized in a yield of 7%.

[0336]

[0337] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -169.48 to -169.80 (m, 1F).

[0338] Example 61 A primary alkylamine represented by formula (b-1) was reacted with a compound represented by the following formula (b ＊ ​​The reaction was carried out in the same manner as in Example 1, except that the primary alkylamine represented by the following formula (d ＊ The reaction product represented by formula (61) was obtained.

[0339]

[0340]

[0341] [Example 62] The above formula (b ＊ -61) and tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, ＊ A fluorinated alkyl compound represented by the formula (I)-62 was synthesized in a yield of 20%.

[0342]

[0343] １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -183.14 to -183.74 (m, 1F).

[0344] Example 63 A reaction was carried out in the same manner as in Example 1, except that 1,1,2,2-tetrafluoroethane-1,2-disulfonyl fluoride represented by the following formula (a-63) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0345] Example 64 Using the primary alkylamine represented by formula (b-1) above, tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and 1,1,2,2-tetrafluoroethane-1,2-disulfonyl fluoride instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride, the alkyl fluoride compound represented by formula (d-4) above was synthesized. The yield was 31%.

[0346] ​Example 65 A reaction was carried out in the same manner as in Example 1, except that 2,2,3,3,4,4-hexafluoro-4-(fluorosulfonyl)butanoyl fluoride represented by the following formula (a-111) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0347] Example 66 Using the primary alkylamine represented by formula (b-1) above, tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and 2,2,3,3,4,4-hexafluoro-4-(fluorosulfonyl)butanoyl fluoride instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride, the alkyl fluoride compound represented by formula (d-4) above was synthesized. The yield was 3%.

[0348] Example 67 A primary alkylamine represented by the above formula (b-1) was reacted with 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride as an amino group leaving group agent to obtain a reaction precursor represented by the following formula (e-67), which was isolated and then reacted with TBAT to synthesize a fluorinated alkyl compound represented by the above formula (d-4).

[0349]

[0350]

[0351] Under a nitrogen atmosphere, 3-amino-1-phenylbutane (149.2 mg, 1.0 mmol) and 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (379.4 mg, 1.2 mmol) were added to diisopropyl ether (20 mL). Triethylamine (151.8 mg, 1.5 mmol) was slowly added to the mixture, and the mixture was stirred at room temperature for 27 hours. The mixture was then quenched with 2 M aqueous hydrochloric acid (20 mL). Chloroform (20 mL) was added to the resulting reaction solution, and the layers were separated. The organic layer was washed once with 2 M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (20 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane to hexane / ethyl acetate=20 / 1), and the solvent was distilled off under reduced pressure, thereby obtaining the compound represented by the above formula (e-67) in a yield of 36%.

[0352] NMR analysis confirmed that the compound represented by the above formula (e-67) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.32-7.26 (m, 2H), 7.23-7.17 (m, 3H), 5.02-4.99 (m, 1H), 3.79-3.74 (m, 1H), 2.75-2.68 (m, 2H), 1.92-1.86 (m, 2H), 1.34 (d, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -46.76 to -46.69 (m, 1F), -107.22 to -107.35 (m, 2F), -112.40 to -112.63 (m, 2F), -118.38 to -118.49 (m, 2F).

[0353] Subsequently, under a nitrogen atmosphere, the compound represented by formula (e-67) (160.3 mg, 0.36 mmol) and TBAT (97.2 mg, 0.18 mmol) were added to toluene (7.2 mL). DBU (54.8 mg, 0.18 mmol) was slowly added thereto, and the mixture was stirred at 110°C for 1 hour, followed by quenching with 2 M aqueous hydrochloric acid (10 mL). Chloroform (10 mL) was added to the resulting reaction solution, followed by phase separation. The organic layer was washed once with 2 M aqueous hydrochloric acid (10 mL), and then washed twice with saturated aqueous sodium carbonate (10 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was then distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography, and the solvent was distilled off under reduced pressure, yielding the compound represented by formula (d-4) in 68% yield.

[0354] NMR analysis confirmed that the compound represented by the above formula (d-4) was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.31-7.18 (m, 5H), 4.75-4.56 (m, 1H), 2.84-2.65 (m, 2H), 2.05-1.70 (m, 2H), 1.55-1.37 (m, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -174.04 to -174.36 (m, 1F).

[0355] Example 68 A reaction precursor represented by the following formula (f-68) was synthesized by reacting a primary alkylamine represented by the following formula (b-68) with 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride as an amino group leaving group agent.

[0356]

[0357]

[0358] Under a nitrogen atmosphere, 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride (10.0 g, 31.6 mmol) was added to acetonitrile (38 mL) and cooled to 0° C. A mixture of propylamine (5.61 g, 94.9 mmol) and acetonitrile (13 mL) was slowly added thereto, and the mixture was stirred at room temperature for 1 hour, and then the reaction solution was filtered.

[0359] Water (100 mL) and chloroform (50 mL) were added to the obtained reaction solution, and the layers were separated. The organic layer was then washed twice with water (50 mL), and the obtained organic layer was washed once with saturated aqueous sodium carbonate solution (50 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was then distilled off under reduced pressure. The obtained crude product was distilled under reduced pressure to obtain the compound represented by formula (f-68) above in 85% yield. NMR analysis confirmed that the reaction precursor represented by formula (f-68) above was obtained. １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 3.99 (t, 2H), 1.87 (qt, 2H), 1.03 (t, 3H).

[0360] Example 69 A reaction precursor represented by the above formula (f-68), which was obtained by reacting a primary alkylamine represented by the above formula (b-68) with 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride as an amino group leaving group agent, was isolated and then reacted with various nucleophiles to obtain reaction products represented by the following formula (d-69).

[0361]

[0362] Example 70 Using a reaction precursor obtained from a primary alkylamine represented by formula (b-68) and an amino group leaving group reagent, and tetrabutylammonium iodide as a nucleophile, an alkyl iodide compound represented by formula (d-70) was synthesized in a yield of 80%.

[0363]

[0364] １ H-NMR (400MHz, CDCl ３ ​) δ (ppm) = 3.16 (t, 2H), 1.82 (qt, 2H), 0.98 (t, 3H).

[0365] Example 71 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group reagent, phenol as a nucleophile, and sodium hydride, an ether compound represented by the following formula (d-71) was synthesized in a yield of 91%.

[0366]

[0367] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.47 to 7.43 (m, 2H), 7.40 to 7.36 (m, 1H), 7.31 to 7.26 (m, 2H), 3.32 (t, 2H), 1.64 (qt, 2H), 0.98 (t, 3H).

[0368] Example 72 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group agent, 4-methylbenzenethiol and sodium hydride as a nucleophile, a sulfide compound represented by the following formula (d-72) was synthesized. The yield was 20%.

[0369]

[0370] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.25 (d, 2H), 7.09 (d, 2H), 2.85 (t, 2H), 2.32 (s, 3H), 1.69 to 1.60 (m, 2H), 1.00 (t, 3H).

[0371] Example 73 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group reagent, and aniline as a nucleophile, an amine compound represented by the following formula (d-73) was synthesized in a yield of 22%.

[0372]

[0373] １ H-NMR (400MHz, CDCl ３ ​​​) δ (ppm) = 7.35-7.31 (m, 2H), 7.08-7.06 (m, 1H), 6.99-6.96 (m, 2H), 3.51 (s, 1H), 3.24-3.21 (m, 2H), 1.70-1.63 (m, 2H), 0.98 (t, 3H).

[0374] Example 74 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group agent, a reaction was carried out in the same manner as in Example 70, except that diethyl malonate and sodium hydride were used as nucleophiles, to synthesize an alkyl compound represented by the following formula (d-74). The yield was 92%.

[0375]

[0376] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 4.19 (q, 4H), 3.33 (t, 1H), 1.91 to 1.85 (m, 2H), 1.39 to 1.33 (m, 2H), 1.27 (t, 6H), 0.94 (t, 3H).

[0377] Example 75 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group agent, a reaction was carried out in the same manner as in Example 70, except that potassium trifluoromethanesulfonamide and potassium fluoride were used as nucleophiles, and acetonitrile was used as the solvent instead of toluene, to synthesize an alkyl compound represented by the following formula (d-75). The yield was 81%.

[0378]

[0379] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 3.02 to 2.98 (m, 2H), 1.54 to 1.45 (m, 2H), 0.90 (t, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -74.36 (s, 3F).

[0380] ​​Example 76 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group reagent, and triethylamine as a nucleophile, a quaternary ammonium compound represented by the following formula (d-76) was synthesized in a yield of 97%.

[0381]

[0382] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 3.31 to 3.26 (m, 6H), 3.09 to 3.05 (m, 2H), 1.74 to 1.68 (m, 2H), 1.38 to 1.31 (m, 9H), 1.05 (t, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -119.20 to -119.65 (m, 4F), -125.87 to -126.42 (m, 2F).

[0383] Example 77 Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group reagent, and 1-methylimidazole as a nucleophile, an imidazolium salt represented by the following formula (d-77) was synthesized in a yield of 98%.

[0384]

[0385] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 8.73 (s, 1H), 7.29 to 7.27 (m, 2H), 4.15 (t, 2H), 3.95 (s, 3H), 1.91 (qt, 2H), 0.98 (t, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -119.26 to -119.66 (m, 4F), -125.88 to -126.30 (m, 2F).

[0386] [Example 78] Using a reaction precursor obtained from a primary alkylamine represented by the above formula (b-68) and an amino group leaving group agent, and triphenylphosphine as a nucleophile, a phosphonium salt represented by the following formula (d-78) was synthesized. The yield was 52%. ​​

[0387]

[0388] １ H-NMR (400MHz, CDCl ３ ) δ (ppm) = 7.84-7.80 (m, 3H), 7.74-7.63 (m, 12H), 3.19-3.12 (m, 2H), 1.75-1.64 (m, 2H), 1.20-1.16 (m, 3H). １９ F-NMR (376MHz, CDCl ３ ) δ (ppm) = -119.27 to -119.50 (m, 4F), -125.83 to -126.47 (m, 2F).

[0389] Comparative Example 1 The reaction was carried out in the same manner as in Example 1, except that 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride was not used.

[0390] Comparative Example 2: Using the primary alkylamine represented by formula (b-1) above, a reaction was carried out using tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile without adding 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. No fluorinated alkyl compound represented by formula (d-4) above was produced.

[0391] Comparative Example 3 A reaction was carried out in the same manner as in Example 1, except that p-toluenesulfonyl chloride represented by the following formula (a'-3) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0392]

[0393] Comparative Example 4 A reaction was carried out using the primary alkylamine represented by the above formula (b-1), tetrabutylammonium iodide as a nucleophile, and p-toluenesulfonyl chloride represented by the above formula (a'-3) in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. No alkyl iodide compound represented by the above formula (d-1) was produced.

[0394] ​Comparative Example 5 A reaction was carried out in the same manner as in Example 1, except that nonafluoro-1-butanesulfonyl fluoride represented by the following formula (a'-5) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0395]

[0396] Comparative Example 6 A reaction was carried out using the primary alkylamine represented by formula (b-1) above, tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and nonafluoro-1-butanesulfonyl fluoride represented by formula (a'-5) above in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. The alkyl fluoride compound represented by formula (d-4) above was not produced.

[0397] Comparative Example 7 A reaction was carried out in the same manner as in Example 1, except that trifluoromethanesulfonic anhydride represented by the following formula (a'-7) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0398]

[0399] Comparative Example 8 A reaction was carried out using the primary alkylamine represented by the above formula (b-1), tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and trifluoromethanesulfonic anhydride represented by the above formula (a'-7) in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. The alkyl fluoride compound represented by the above formula (d-4) was not produced.

[0400] Comparative Example 9 A reaction was carried out in the same manner as in Example 1, except that propane-1,3-disulfonyl fluoride represented by the following formula (a'-9) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0401]

[0402] Comparative Example 10: A reaction was carried out using the primary alkylamine represented by formula (b-1) above, tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and propane-1,3-disulfonyl fluoride represented by formula (a'-9) above in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. The alkyl fluoride compound represented by formula (d-4) above was not produced.

[0403] Comparative Example 11 A reaction was carried out in the same manner as in Example 1, except that propane-1,3-disulfonyl chloride represented by the following formula (a'-10) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0404]

[0405] Comparative Example 12 A reaction was carried out using the primary alkylamine represented by the above formula (b-1), tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and propane-1,3-disulfonyl chloride represented by the above formula (a'-11) in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. The alkyl fluoride compound represented by the above formula (d-4) was not produced.

[0406] Comparative Example 13 A reaction was carried out in the same manner as in Example 1, except that 1,2-benzenedisulfonyl fluoride represented by the following formula (a'-13) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0407]

[0408] Comparative Example 14 A reaction was carried out using the primary alkylamine represented by the above formula (b-1), tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and 1,2-benzenedisulfonyl fluoride represented by the above formula (a'-13) in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. The alkyl fluoride compound represented by the above formula (d-4) was not produced.

[0409] Comparative Example 15 A reaction was carried out in the same manner as in Example 1, except that 1,2-benzenedisulfonyl chloride represented by the following formula (a'-15) was used instead of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride.

[0410]

[0411] Comparative Example 16: A reaction was carried out using the primary alkylamine represented by the above formula (b-1), tetrabutylammonium difluorotriphenylsilicate (TBAT) as a nucleophile, and 1,2-benzenedisulfonyl chloride represented by the above formula (a'-15) in place of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl fluoride. The alkyl fluoride compound represented by the above formula (d-4) was not produced.

[0412] According to the present invention, it is possible to provide an amino leaving group agent for efficiently producing a reaction product by reacting an amino group-containing organic compound with an amino leaving group agent and then reacting the resulting compound with a nucleophile, a method for producing a reaction product, a reaction precursor, a method for producing a reaction precursor, and a method for producing an optically active reaction product. Thus, the present invention is industrially applicable.

Claims

1. An amino group leaving group generating agent comprising a compound (a) represented by the following formula (a), for producing a reaction product by reacting the amino group leaving group generating agent with an organic compound having an amino group and further reacting the resulting compound with a nucleophile. １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ each independently represents a carbonyl group or a sulfonyl group; Y １ and Y ２ each independently represents a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

2. The amino group leaving group agent according to claim 1, wherein the organic compound is represented by the following formula (b): In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

3. The amino leaving group agent according to claim 1, wherein the nucleophile is used to replace the amino group that has reacted with the amino leaving group agent with a chemical species, and the chemical species comprises at least one selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amide group, a substituted or unsubstituted sulfonamide group, and a substituted or unsubstituted hydrocarbon group.

4. The amino group leaving group agent according to any one of claims 1 to 3, wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

5. A method for producing a reaction product, comprising reacting an amino group-containing organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a), and further reacting the compound with a nucleophile. １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ each independently represents a carbonyl group or a sulfonyl group; Y １ and Y ２ each independently represents a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

6. The method for producing a reaction product according to claim 5, wherein the organic compound is represented by the following formula (b): In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

7. The method for producing a reaction product according to claim 5, wherein the nucleophile is used to replace the amino group that has reacted with the amino group leaving group agent with a chemical species, and the chemical species comprises at least one selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amide group, a substituted or unsubstituted sulfonamide group, and a substituted or unsubstituted hydrocarbon group.

8. A method for producing a reaction product according to any one of claims 5 to 7, wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

9. A reaction precursor comprising a compound (e) represented by the following formula (e) or a compound (f) represented by the following formula (f) for obtaining a reaction product by reacting with a nucleophile: In the above formulas (e) and (f), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; １ and X ２ each independently represents a carbonyl group or a sulfonyl group; Y ２ is a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group; M １ is a hydrogen atom or a counter ion; R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

10. The reaction precursor according to claim 9, wherein the nucleophile is used to replace the tertiary amino groups in the above formulae (e) and (f) with a chemical species, and the chemical species comprises at least one chemical species selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amide group, a substituted or unsubstituted sulfonamide group, and a substituted or unsubstituted hydrocarbon group.

11. The reaction precursor according to claim 9 or 10, wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

12. A method for producing a reaction precursor containing a compound (e) represented by the following formula (e) or a compound (f) represented by the following formula (f) for obtaining a reaction product by reacting with a nucleophile, the method comprising reacting an amino group-containing organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a): １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ each independently represents a carbonyl group or a sulfonyl group; Y １ and Y ２ each independently represents a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group. In the above formulas (e) and (f), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; １ and X ２ each independently represents a carbonyl group or a sulfonyl group; Y ２ is a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group; M １ is a hydrogen atom or a counter ion; R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

13. The method for producing a reaction precursor according to claim 12, wherein the organic compound is represented by the following formula (b): In the above formula (b), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ At least two of these may be bonded to each other to form a ring.

14. The method for producing a reaction precursor according to claim 12, wherein the nucleophile is used to replace the amino group that has reacted with the amino group leaving group agent with a chemical species, and the chemical species includes at least one chemical species selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amide group, a substituted or unsubstituted sulfonamide group, and a substituted or unsubstituted hydrocarbon group.

15. The method for producing a reaction precursor according to any one of claims 12 to 14, wherein the reaction product is represented by the following formula (d): In the above formula (d), R １ , R ２ and R ３ are each independently a hydrogen atom, a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ , R ２ and R ３ at least two of these may be bonded to each other to form a ring; Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

16. A method for producing an optically active reaction product, comprising reacting an amino group-containing optically active organic compound with an amino group-leaving agent containing a compound (a) represented by the following formula (a), and further reacting the compound with a nucleophile: １ -X １ -Rf-X ２ -Y ２ In the above formula (a), Rf is a substituted or unsubstituted divalent hydrocarbon group containing at least one fluorine atom; X １ and X ２ each independently represents a carbonyl group or a sulfonyl group; Y １ and Y ２ each independently represents a halogen atom, a substituted or unsubstituted alkylcarbonyloxy group, a substituted or unsubstituted arylcarbonyloxy group, a substituted or unsubstituted alkylsulfonyloxy group, or a substituted or unsubstituted arylsulfonyloxy group.

17. The optically active organic compound is represented by the following formula (b ＊ 17. The method for producing the optically active reaction product according to claim 16, The above formula (b ＊ ) Medium, R １ and R ２ are not the same and each independently represents a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ and R ２ may be bonded to each other to form a ring.

18. A method for producing an optically active reaction product according to claim 16, wherein the nucleophile is used to replace the amino group that has reacted with the amino group leaving group agent with a chemical species, and the chemical species comprises at least one chemical species selected from the group consisting of a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amide group, a substituted or unsubstituted sulfonamide group, and a substituted or unsubstituted hydrocarbon group.

19. The optically active reaction product is represented by the following formula (d ＊ The method for producing the optically active reaction product according to any one of claims 16 to 18, The above formula (d ＊ ) Medium, R １ and R ２ are not the same and each independently represents a polar group, a substituted or unsubstituted saturated hydrocarbon group, a substituted or unsubstituted unsaturated hydrocarbon group, or a substituted or unsubstituted aromatic hydrocarbon group; R １ and R ２ may be bonded to each other to form a ring; Nu is a hydrogen atom, a hydroxyl group, a halogen atom, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an azido group, a substituted or unsubstituted amino group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a cyano group, a substituted or unsubstituted phosphino group, a substituted or unsubstituted amido group, a substituted or unsubstituted sulfonamido group, or a substituted or unsubstituted hydrocarbon group.

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