Method for producing carbamoyl fluoride

Abstract

The present invention relates to a method for producing carbamoyl fluoride, etc., characterized by obtaining carbamoyl fluoride by reacting a secondary amine with CF3SO2Na, and by establishing reaction conditions under an oxygen atmosphere along with light irradiation in the presence of a DDQ catalyst, various carbamoyl fluorides can be synthesized from a secondary amine in an environmentally friendly manner and with excellent yield.

Description

Technology Field

[0001] The present invention relates to a novel method for manufacturing carbamoyl fluoride, etc. Background Technology

[0003] Carbamoyl fluoride is FC(=O)-NR 1 R 2 It refers to a compound having the general formula. Conventional methods for synthesizing carbamoyl fluoride include a method using difluorocarbene in situ (Dusty Cadwallader et al., Synthesis of Carbamoyl Fluorides Using a Difluorophosgene Surrogate Derived from Difluorocarbene and Pyridine N-Oxides), a method of synthesis from trifluoromethanesulfonate through click chemistry (Hai-Xia Song et al., Concise and Additive-Free Click Reactions between Amines and CF3SO3CF3), and a method in which carbamoyl fluoride is synthesized by the reaction of difluorocarbene and hydroxylamine (Hannah Baars et al., The Reactivity of Difluorocarbene with Hydroxylamines: Synthesis of Carbamoyl Fluorides).

[0004] Conventional technologies use various reagents or reactants as sources of FC=O, mostly generating intermediates in situ or using CO2 gas, and there is a need for a method to synthesize carbamoyl fluoride in an environmentally friendly and high-yield manner. The problem to be solved

[0006] The technical problem that the present invention aims to solve is to provide a method for manufacturing carbamoyl fluoride.

[0007] In addition, another objective of the present invention is to provide a carbamoyl fluoride compound produced by the above-described manufacturing method.

[0008] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by a person skilled in the art from the description below. means of solving the problem

[0010] To solve the above problem, the present invention provides a method for preparing a compound represented by Formula 1, comprising the step of reacting a compound represented by Formula 2 below with CF3SO2Na:

[0011] [Chemical Formula 2]

[0012]

[0013] [Chemical Formula 1]

[0014]

[0015] In the above Chemical Formula 1 and Chemical Formula 2,

[0016] R 1 and R 2 Each independently, alkyl group, alkenyl group, alkynyl group, , selected from the group consisting of substituted or unsubstituted benzyl groups, substituted or unsubstituted phenethyl groups and substituted or unsubstituted naphthyl groups, or combined with each other to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl, and

[0017] The above-mentioned substituted benzyl group, phenethyl group and naphthyl group are substituted with alkyl, -CF3, cyano, or alkoxy groups, and

[0018] The above-mentioned substituted heterocycloalkyl or heteroaryl is substituted with alkyl, alkoxy, halogen, substituted or unsubstituted phenyl or pyridyl, and

[0019] The above-mentioned substituted phenyl is substituted with an alkoxy or -CF3.

[0020] According to one side, the above R 1 and R 2 The heterocycloalkyl group formed by bonding together is any one selected from piperidine, piperazine, and azephan, and

[0021] The above R 1 and R 2 Heteroaryls formed by the bonding of each other or It could be.

[0022] According to one aspect, the substituted heterocycloalkyl or heteroaryl may be substituted with methyl, methoxy, fluoro, chloro, phenyl, tert-butoxycarbonyl, methoxyphenyl, trifluorophenyl, or pyridyl.

[0023] According to one side, the above R 1 and R 2 Each independently, a methyl group, an isopropyl group, an allyl group, , , , , , , , and It can be any one selected from the group consisting of

[0024] According to one side, the above [Chemical Formula 1] may be any one selected from the group consisting of the following:

[0025] [Chemical Formula 1-1]

[0026] ,

[0027] [Chemical Formula 1-2]

[0028] ,

[0029] [Chemical Formula 1-3]

[0030] ,

[0031] [Chemical Formula 1-4]

[0032] ,

[0033] [Chemical Formula 1-5]

[0034] ,

[0035] [Chemical Formula 1-6]

[0036] ,

[0037] [Chemical Formula 1-7]

[0038] ,

[0039] [Chemical Formula 1-8]

[0040] ,

[0041] [Chemical Formula 1-9]

[0042] ,

[0043] [Chemical Formula 1-10]

[0044] ,

[0045] [Chemical Formula 1-11]

[0046] ,

[0047] [Chemical Formula 1-12]

[0048] ,

[0049] [Chemical Formula 1-13]

[0050] ,

[0051] [Chemical Formula 1-14]

[0052] ,

[0053] [Chemical Formula 1-15]

[0054] ,

[0055] [Chemical Formula 1-16]

[0056] ,

[0057] [Chemical Formula 1-17]

[0058] ,

[0059] [Chemical Formula 1-18]

[0060] ,

[0061] [Chemical Formula 1-19]

[0062] ,

[0063] [Chemical Formula 1-20]

[0064] ,

[0065] [Chemical Formula 1-21]

[0066] ,

[0067] [Chemical Formula 1-22]

[0068] ,

[0069] [Chemical Formula 1-23]

[0070] ,

[0071] [Chemical Formula 1-24]

[0072] ,

[0073] [Chemical Formula 1-25]

[0074] and

[0075] [Chemical Formula 1-26]

[0076] .

[0077] According to one side, the above reaction may be carried out using DDQ (2,3-Dichloro-5,6-dicyano-1,4-benzoquinone) as a catalyst and under light irradiation conditions.

[0078] According to one side, the above reaction may take place under an oxygen atmosphere.

[0079] According to one side, the reaction may be carried out in the presence or absence of TFA (Trifluoroacetic acid).

[0080] According to another embodiment of the present invention, a carbamoyl fluoride compound represented by the following chemical formula 1, prepared by the above manufacturing method, is provided:

[0081] [Chemical Formula 1]

[0082]

[0083] In the above chemical formula 1,

[0084] R 1 and R 2 Each independently, alkyl group, alkenyl group, alkynyl group, , selected from the group consisting of substituted or unsubstituted benzyl groups, substituted or unsubstituted phenethyl groups and substituted or unsubstituted naphthyl groups, or combined with each other to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl, and

[0085] The above-mentioned substituted benzyl group, phenethyl group and naphthyl group are substituted with alkyl, -CF3, cyano, or alkoxy groups, and

[0086] The above-mentioned substituted heterocycloalkyl or heteroaryl is substituted with alkyl, alkoxy, halogen, substituted or unsubstituted phenyl or pyridyl, and

[0087] The above-mentioned substituted phenyl is substituted with an alkoxy or -CF3.

[0088] According to one aspect, the carbamoyl fluoride compound represented by [Chemical Formula 1] above may be any one selected from the group consisting of the following:

[0089] [Chemical Formula 1-1]

[0090] ,

[0091] [Chemical Formula 1-2]

[0092] ,

[0093] [Chemical Formula 1-3]

[0094] ,

[0095] [Chemical Formula 1-4]

[0096] ,

[0097] [Chemical Formula 1-5]

[0098] ,

[0099] [Chemical Formula 1-6]

[0100] ,

[0101] [Chemical Formula 1-7]

[0102] ,

[0103] [Chemical Formula 1-8]

[0104] ,

[0105] [Chemical Formula 1-9]

[0106] ,

[0107] [Chemical Formula 1-10]

[0108] ,

[0109] [Chemical Formula 1-11]

[0110] ,

[0111] [Chemical Formula 1-12]

[0112] ,

[0113] [Chemical Formula 1-13]

[0114] ,

[0115] [Chemical Formula 1-14]

[0116] ,

[0117] [Chemical Formula 1-15]

[0118] ,

[0119] [Chemical Formula 1-16]

[0120] ,

[0121] [Chemical Formula 1-17]

[0122] ,

[0123] [Chemical Formula 1-18]

[0124] ,

[0125] [Chemical Formula 1-19]

[0126] ,

[0127] [Chemical Formula 1-20]

[0128] ,

[0129] [Chemical Formula 1-21]

[0130] ,

[0131] [Chemical Formula 1-22]

[0132] ,

[0133] [Chemical Formula 1-23]

[0134] ,

[0135] [Chemical Formula 1-24]

[0136] ,

[0137] [Chemical Formula 1-25]

[0138] and

[0139] [Chemical Formula 1-26]

[0140] . Effects of the invention

[0142] The present invention relates to a method for producing carbamoyl fluoride, etc., wherein CF3SO2Na is used as a source of FC=O, light irradiation is performed in the presence of a DDQ catalyst, and reaction conditions under an oxygen atmosphere are established, thereby enabling the synthesis of various carbamoyl fluorides from secondary amines in an environmentally friendly manner and with excellent yield. Specific details for implementing the invention

[0144] As a result of researching a novel method for producing carbamoyl fluoride, the inventors intend to provide the invention by using CF3SO2Na as a source of C=O, performing light irradiation in the presence of a DDQ catalyst, and establishing reaction conditions under an oxygen atmosphere.

[0145] The present invention provides a method for preparing a compound represented by Formula 1, comprising the step of reacting a compound represented by Formula 2 below with CF3SO2Na:

[0146] [Chemical Formula 2]

[0147]

[0148] [Chemical Formula 1]

[0149]

[0150] In the above Chemical Formula 1 and Chemical Formula 2,

[0151] R 1 and R 2 Each independently, alkyl group, alkenyl group, alkynyl group, , selected from the group consisting of substituted or unsubstituted benzyl groups, substituted or unsubstituted phenethyl groups and substituted or unsubstituted naphthyl groups, or combined with each other to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl, and

[0152] The above-mentioned substituted benzyl group, phenethyl group and naphthyl group are substituted with alkyl, -CF3, cyano, or alkoxy groups, and

[0153] The above-mentioned substituted heterocycloalkyl or heteroaryl is substituted with alkyl, alkoxy, halogen, substituted or unsubstituted phenyl or pyridyl, and

[0154] The above-mentioned substituted phenyl is substituted with an alkoxy or -CF3.

[0155] In the present invention, the term “substitution” refers to a reaction that replaces an atom or atomic group contained in a molecule of a compound with another atom or atomic group.

[0156] The term “alkyl group” as used in the present invention refers to a branched or straight-chain substituent as a saturated hydrocarbon. Preferably, it may be a methyl group, but is not limited thereto.

[0157] The term “alkenyl group” as used in the present invention refers to a substituent having one or more carbon-carbon double bonds as an unsaturated hydrocarbon.

[0158] The term “alkynyl group” as used in the present invention refers to a substituent having one or more carbon-carbon triple bonds as an unsaturated hydrocarbon.

[0159] The term “benzyl group” as used in this invention refers to a substituent in which -CH2 is bonded to a benzene ring, meaning a substituent having a C6H5CH2- structure.

[0160] The term “phenetyl group” as used in this invention refers to a substituent in which -C2H4 is bonded to a benzene ring, meaning a substituent having a C6H5CH2CH2- structure.

[0161] The term “naphthyl group” used in the present invention refers to a substituent from which one hydrogen is removed from naphthalene.

[0162] The term “heterocycloalkyl” used in the present invention refers to a saturated hydrocarbon group with a single bond in a ring shape containing one or more heteroatoms such as N, O, or S, and depending on the number and type of heteroatoms included in the ring and the number of carbon atoms, there are aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, etc.

[0163] The term "aryl" used in the present invention refers to an aromatic substituent having at least one ring having a shared pi electron system, such as phenyl, benzyl, etc.

[0164] The term “heteroaryl” used in the present invention refers to an aromatic ring compound containing one or more heteroatoms such as N, O, or S, and depending on the number and type of heteroatoms included in the ring and the number of carbon atoms, there are pyrroleyl, furanyl, pyridinyl, pyrimidinyl, pyranyl, etc.

[0165] According to one side, the above R 1 and R 2 The heterocycloalkyl group formed by bonding together is any one selected from piperidine, piperazine, and azephan, and

[0166] The above R 1 and R 2 Heteroaryls formed by the bonding of each other or It could be.

[0167] According to one aspect, the substituted heterocycloalkyl or heteroaryl may be substituted with methyl, methoxy, fluoro, chloro, phenyl, tert-butoxycarbonyl, methoxyphenyl, trifluorophenyl, or pyridyl.

[0168] According to one side, the above R 1 and R 2 Each independently, a methyl group, an isopropyl group, an allyl group, , , , , , , , and It can be any one selected from the group consisting of

[0169] According to one side, the above [Chemical Formula 1] may be any one selected from the group consisting of the following:

[0170] [Chemical Formula 1-1]

[0171] ,

[0172] [Chemical Formula 1-2]

[0173] ,

[0174] [Chemical Formula 1-3]

[0175] ,

[0176] [Chemical Formula 1-4]

[0177] ,

[0178] [Chemical Formula 1-5]

[0179] ,

[0180] [Chemical Formula 1-6]

[0181] ,

[0182] [Chemical Formula 1-7]

[0183] ,

[0184] [Chemical Formula 1-8]

[0185] ,

[0186] [Chemical Formula 1-9]

[0187] ,

[0188] [Chemical Formula 1-10]

[0189] ,

[0190] [Chemical Formula 1-11]

[0191] ,

[0192] [Chemical Formula 1-12]

[0193] ,

[0194] [Chemical Formula 1-13]

[0195] ,

[0196] [Chemical Formula 1-14]

[0197] ,

[0198] [Chemical Formula 1-15]

[0199] ,

[0200] [Chemical Formula 1-16]

[0201] ,

[0202] [Chemical Formula 1-17]

[0203] ,

[0204] [Chemical Formula 1-18]

[0205] ,

[0206] [Chemical Formula 1-19]

[0207] ,

[0208] [Chemical Formula 1-20]

[0209] ,

[0210] [Chemical Formula 1-21]

[0211] ,

[0212] [Chemical Formula 1-22]

[0213] ,

[0214] [Chemical Formula 1-23]

[0215] ,

[0216] [Chemical Formula 1-24]

[0217] ,

[0218] [Chemical Formula 1-25]

[0219] and

[0220] [Chemical Formula 1-26]

[0221] .

[0222] According to one side, the above reaction may be carried out using DDQ (2,3-Dichloro-5,6-dicyano-1,4-benzoquinone) as a catalyst and under light irradiation conditions.

[0223] According to one side, the above reaction may take place under an oxygen atmosphere.

[0224] In this invention, it was confirmed that carbamoyl fluoride can be synthesized in excellent yield when reacting a secondary amine with CF3SO2Na under DDQ catalyst, light irradiation conditions, and an oxygen atmosphere, and this was completed as an invention as disclosed in Examples 1 and 2 below.

[0225] According to one aspect, the reaction may be carried out in the presence or absence of TFA (Trifluoroacetic acid). Depending on the presence or absence of TFA, the reaction conditions may be acidic or acid-free, and a suitable method may be selected depending on the secondary amine that is the reactant. The presence or absence of TFA depending on the specific reactant is disclosed in each of the following Examples 2.

[0226] The present invention is capable of various modifications and may have various embodiments. Specific embodiments are illustrated in the drawings and described in detail in the detailed description below. However, this is not intended to limit the present invention to specific embodiments, and it should be understood that it includes all modifications, equivalents, and substitutions that fall within the spirit and scope of the present invention. In describing the present invention, detailed descriptions of related prior art are omitted if it is determined that such detailed descriptions may obscure the essence of the present invention.

[0228] Example 1. Method for synthesizing carbamoyl fluoride

[0229] Carbamoyl fluoride was synthesized as follows under conditions without TFA (Trifluoroacetic acid) (hereinafter Method A). In a round-bottom flask, sodium trifluoromethanesulfinate (4.0 mmol, 4.0 equiv), amine (1 mmol, 1.0 equiv), and 0.2 mol% 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) were dissolved in acetonitrile (0.05 M). The mixed solution was irradiated with a blue LED and stirred at room temperature for 2 hours. After confirming the completion of the reaction by TLC, an aqueous solution of sodium bicarbonate (NaHCO3) was added to the mixed solution, and the mixture was extracted with methylene chloride (3 x 10 mL). The organic layer was washed with water and brine, dried with MgSO4, and then the solvent was removed under reduced pressure. The concentrated mixture was purified by silica gel tube chromatography to obtain a carbamoyl fluoride product.

[0230] Carbamoyl fluoride was synthesized as follows under conditions in the presence of TFA (hereinafter Method B). Sodium trifluoromethanesulfinate (4.0 mmol, 4.0 equiv), amine (1 mmol, 1.0 equiv), 0.2 mol% 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), and trifluoroacetic acid (2.0 mmol, 2.0 equiv) were dissolved in acetonitrile (0.05 M) in a flame-dried round-bottom flask. The mixed solution was irradiated with a blue LED and stirred at room temperature for 2 hours. After confirming the completion of the reaction by TLC, an aqueous sodium bicarbonate (NaHCO3) solution was added to the mixed solution, and the mixture was extracted with methylene chloride (3 x 10 mL). The organic layer was washed with water and brine, dried with MgSO4, and then the solvent was removed under reduced pressure. The concentrated mixture was purified by silica gel column chromatography to obtain the carbamoyl fluoride product.

[0232] Example 2. Synthesis of Carbamoyl Fluoride

[0233] Example 2-1. Synthesis of 6,7-Dimethoxy-3,4-dihydroisoquinoline-2(1H)-carbonyl fluoride (Formula 1-1)

[0234]

[0235] It was synthesized by method A of Example 1 above, and obtained as a white solid with a yield of 50 mg, 80%.

[0236] Column chromatography (hexane / EtOAc = 10:1)

[0237] 1 H-NMR (400 MHz, CDCl3) δ 6.62 (d, J = 3.6 Hz, 1H), 6.56 (d, J = 11.9 Hz, 1H), 4.54 (s, 2H). 3.84 (d, J = 3.0 Hz, 6H), 3.69 - 3.64 (m, 2H), 2.84 (m, 2H).

[0238] 19 F-NMR (376MHz, CDCl3) δ -20.27, -23.66.

[0239] 13 C-NMR (100 MHz, CDCl3) δ 148.10, 148.05, 148.03, 148.00, 146.8 (d, 1 J = 286.4 Hz), 146.6 (d, 1 J = 286.2 Hz), 125.6, 125.4, 123.5, 123.2, 111.5, 111.4, 109.0, 108.8, 56.01, 55.98, 46.3 (d, 3 J = 1.5 Hz), 45.8 (d, 3 J = 4.2 Hz), 42.8 (d, 3 J = 1.4 Hz), 42.6 (d, 3 J = 3.5 Hz), 28.3, 27.7.

[0240] HRMS(ESI) (m / z) calcd for C12H14FNO3 [M+Na]+ 262.0850, found 262.0852.

[0242] Example 2-2. Synthesis of 6-Methoxy-3,4-dihydroisoquinoline-2(1H)-carbonyl fluoride (Formula 1-2)

[0243]

[0244] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 30 mg, 47%.

[0245] Column chromatography (hexane / EtOAc = 10:1)

[0246] 1H-NMR (400 MHz, CDCl3) δ 7.05-7.00 (m, 1H), 6.80-6.77 (m, 1H), 6.69 (s, 1H), 4.57 (s, 2H), 3.79 (s, 3H), 3.71-3.65 (m, 2H), 2.91-2.86 (m, 2H).

[0247] 13 C-NMR (100 MHz, CDCl3) δ 158.60, 158.56, 146.73 (d, 1 J = 300.6 Hz), 146.72 (d, 1 J = 285.9 Hz), 135.1, 134.9, 127.4, 127.2, 123.9, 123.6, 113.6, 113.5, 113.0, 112.9, 55.3 (2C), 46.1 (d, 3 J = 1.3 Hz), 45.7 (d, 3 J = 4.0 Hz), 42.6 (d, 3 J = 1.2 Hz), 42.4 (d, 3 J = 3.6 Hz), 29.1, 28.5.

[0248] 19 F-NMR (376 MHz, CDCl3) δ -20.34, -23.05.

[0249] HRMS(ESI) (m / z) calcd for C11H12FNO2 [M+Na]+ 232.0744, found 232.0743.

[0251] Example 2-3. Synthesis of 3,4-Dihydroisoquinoline-2(1H)-carbonyl fluoride (Formula 1-3)

[0252]

[0253] It was synthesized by method B of Example 1 above, and obtained as a yellow oil with a yield of 24 mg, 36%.

[0254] Column chromatography (hexane / EtOAc = 10:1)

[0255] 1 H-NMR (400 MHz, CDCl3) δ 7.23-7.09 (m, 4H), {4.64 (s), 4.63 (s), 2H}, 3.74-3.68 (m, 2H), 2.95-2.90 (m, 2H).

[0256] 19 F-NMR (376 MHz, CDCl3) δ -20.23, -23.19.

[0258] Example 2-4. Synthesis of 6-Fluoro-3,4-dihydroisoquinoline-2(1H)-carbonyl fluoride (Formula 1-4)

[0259]

[0260] It was synthesized by method A of Example 1 above, and obtained as a yellow oil with a yield of 17.2 mg, 20%.

[0261] Column chromatography (hexane / EtOAc = 10:1)

[0262] 1 H-NMR (400 MHz, CDCl3) δ 7.11-7.05 (m, 1H), 6.96-6.68 (m, 2H), 4.60 (s, 2H), 3.72-3.67 (m, 2H), 2.94-2.89 (m, 2H).

[0263] 13 C-NMR (100 MHz, CDCl3) δ 161.62 (d, 1 J = 246.4 Hz), 161.59 (d, 1 J = 245.8 Hz), 146.8 (d, 1 J = 257.2 Hz), 146.7 (d, 1 J = 255.6 Hz), 128.5 (d, 3 J = 8.4 Hz), 128.2 (d, 3 J = 7.8 Hz), 127.9 (d, 3 J = 8.4 Hz), 127.7 (d, 3J = 8.5 Hz), 127.4 (d, 4 J = 3.0 Hz), 127.1 (d, 4 J = 2.7 Hz), 115.6 (d, 2 J = 23.4 Hz), 115.2 (d, 2 J = 21.5 Hz), 114.1 (d, 2 J = 22.0 Hz), 114.0 (d, 2 J = 22.0 Hz), 46.1 (d, 3 J = 1.5 Hz), 45.7 (d, 3 J = 4.1 Hz), 42.4 (d, 3 J = 1.4 Hz), 42.1 (d, 3 J = 3.6 Hz), 28.9 (d, 4 J = 1.6 Hz), 28.3 (d, 4 J = 1.4 Hz).

[0264] 19 F-NMR (376MHz, CDCl3) δ -20.21, -23.01, -115.16, -115.25.

[0265] HRMS(ESI) (m / z) calcd for C12H14FNO3 [M+Na]+ 220.0544, found 220.0545.

[0267] Example 2-5. Synthesis of 6-Chloro-3,4-dihydroisoquinoline-2(1H)-carbonyl fluoride (Formula 1-5)

[0268]

[0269] It was synthesized by method A of Example 1 above, and obtained as a yellow oil with a yield of 13 mg, 20%.

[0270] Column chromatography (hexane / EtOAc = 1:1)

[0271] 1 H-NMR (400 MHz, CDCl3) δ 7.21 - 7.17 (m, 2H), 7.07 - 7.02 (m, 1H), 4.59 (s, 2H), 3.72 - 3.66 (m, 2H), 2.92 - 2.87 (m, 2H).

[0272] 13 C-NMR (100 MHz, CDCl3) δ 146.6 (d, 1 J = 286.8 Hz), 146.5 (d, 1 J = 286.4 Hz), 135.6, 135.3, 132.9, 132.8, 130.2, 129.9, 128.8, 128.6, 127.7, 127.5, 127.1, 127.0, 46.2 (d, 3 J = 1.2 Hz), 45.7(d, 3 J = 4.2 Hz), 42.4 (d, 3 J = 1.4 Hz), 42.1 (d, 3 J = 3.6 Hz), 28.6, 28.1.

[0273] 19 F-NMR (376MHz, CDCl3) δ -20.08, -23.07.

[0274] HRMS(ESI) (m / z) calcd for C12H14FNO3 [M+Na]+ 236.0249, found 232.0252.

[0276] Examples 2-6. Synthesis of 4-Phenylpiperidine-1-carbonyl fluoride (Chemical Formula 1-6)

[0277]

[0278] It was synthesized by method A of Example 1 above and obtained as a white solid with a yield of 35 mg, 54%.

[0279] Column chromatography (hexane / EtOAc = 1:1)

[0280] 1 H-NMR (400 MHz, CDCl3) δ 7.34-7.31 (m, 2H), 7.23-7.18 (m, 3H), 4.21 (m, 1H), 4.09 (m, 1H), 3.09-2.97 (m, 2H), 2.75-2.67 (m, 1H), 1.95-1.89 (m, 2H), 1.80-1.65 (m, 2H).

[0281] 19 F-NMR (376 MHz, CDCl3) δ -24.59.

[0283] Example 2-7. Synthesis of tert-Butyl 4-(fluorocarbonyl)piperazine-1-carboxylate (Formula 1-7)

[0284]

[0285] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 37 mg, 50%.

[0286] Column chromatography (hexane / EtOAc = 3:1)

[0287] 1 H-NMR (400 MHz, CDCl3) δ 3.48-3.45 (m, 8H), 1.47 (s, 9H).

[0288] 19 F-NMR (376MHz, CDCl3) δ -23.57.

[0290] Example 2-8. Synthesis of tert-Butyl (R)-4-(fluorocarbonyl)-2-methylpiperazine-1-carboxylate (Formula 1-8)

[0291]

[0292] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 30 mg, 38%.

[0293] Column chromatography (hexane / EtOAc = 3:1)

[0294] 1 H-NMR (400 MHz, CDCl3) δ 4.20-3.66 (m, 4H), 3.26-2.88 (m, 3H), 1.47 (s, 9H), 1.25-1.23 (m, 3H).

[0295] 13 C-NMR (100 MHz, CDCl3) δ 154.8 (2C), 146.4 (d, 1 J = 286.7 Hz), 146.1 (d, 1 J = 287.9 ​​Hz), 80.5 (2C), 48.8 (2C), 48.0, 46.7, 43.4, 42.6, 39.8 (2C), 28.3 (2C), 15.9, 14.8.

[0296] 19 F-NMR (376 MHz, CDCl3) δ -22.30, -22.50, -23.56.

[0297] HRMS(ESI) (m / z) calcd for C12H14FNO3 [M+Na]+ 269.1277, found 269.1278.

[0299] Example 2-9. Synthesis of tert-Butyl 4-(fluorocarbonyl)-1,4-diazepane-1-carboxylate (Formula 1-9)

[0300]

[0301] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 25 mg, 61%.

[0302] Column chromatography (hexane / EtOAc = 3:1)

[0303] 1 H-NMR (400 MHz, CDCl3) δ 3.54-3.40 (m, 8H), 1.95-1.86 (m, 2H), 1.47 (s, 9H).

[0304] 13 C-NMR (100 MHz, CDCl3) δ 155.0 (2C), 147.4 (d, 1 J = 288.7 Hz), 147.0 (d, 1 J= 289.4 Hz), 80.2 (2C), 50.0, 48.9, 48.5, 47.9, 47.4, 46.7, 46.4, 46.1, 28.4 (2C), 27.2, 26.1.

[0305] 19 F-NMR (376 MHz, CDCl3) δ -22.17, 22.38, 22.54.

[0306] HRMS(ESI) (m / z) calcd for C11H19FN2O3 [M+Na]+ 269.1272, found 269.1275.

[0308] Example 2-10. Synthesis of Benzyl(methyl)carbamic fluoride (Chemical Formula 1-10)

[0309]

[0310] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 57 mg, 82%.

[0311] Column chromatography (hexane / EtOAc = 10:1)

[0312] 1 H-NMR (400 MHz, CDCl3) δ 7.40-7.28 (m, 3H), 7.25-7.23 (m, 2H), {4.47 (s), 4.43 (s), 2H},

[0313] {2.92 (s), 2.87 (s), 3H}.

[0314] 19 F-NMR (376 MHz, CDCl3) δ -21.77, -23.43.

[0316] Example 2-11. Synthesis of N-Methyl-1-(2-(trifluoromethyl)phenyl)methanamine (Formula 1-11)

[0317]

[0319] It was synthesized by method A of Example 1 above, and obtained as an orange oil with a yield of 53 mg, 77%.

[0320] Column chromatography (hexane / EtOAc = 10:1)

[0321] 1 H-NMR (400 MHz, CDCl3) δ 7.71-7.68 (m, 1H), 7.62-7.57 (m, 1H), 7.45-7.35 (m, 2H), {4.72

[0322] (s), 4.68 (s), 2H}, {2.96 (s), 2.91 (s), 3H}.

[0323] 13 C-NMR (100 MHz, CDCl3) δ 148.6 (d, 1 J = 287.3 Hz), 147.7 (d, 1 J = 287.2 Hz), 134.1, 134.0, 132.6, 132.5, 129.8 (q, 2 J = 30.3 Hz), 128.5 (q, 2 J = 30.3 Hz), 128.2, 128.0, 127.9, 127.4, 126.4 (q, 3 J = 5.7 Hz), 126.2 (q, 3 J = 5.7 Hz), 124.15 (q, 1 J = 280.1 Hz), 124.12 (q, 1 J = 280.0 Hz), 49.5 (d, 3 J = 3.0 Hz), 49.3 (d, 3 J = 3.1 Hz), 35.4, 34.2 (d, 3 J = 3.7 Hz).

[0324] 19 F-NMR (376 MHz, CDCl3) δ -21.71, -23.41, -59.45, -59.98.

[0325] HRMS(ESI) (m / z) calcd for C10H9F4NO [M+Na]+ 258.0512, found 258.0513.

[0327] Example 2-12. Synthesis of (4-Cyanobenzyl)(methyl)carbamic fluoride (Chemical Formula 1-12)

[0328]

[0329] It was synthesized by method A of Example 1 above, and obtained as an orange oil with a yield of 35 mg, 67%.

[0330] Column chromatography (hexane / EtOAc = 10:1)

[0331] 1 H-NMR (400 MHz, CDCl3) δ 7.67-7.64 (m, 2H), 7.40-7.33 (m, 2H), {4.51 (s), 4.48 (s), 2H},

[0332] {2.95 (s), 2.91 (s), 2H}.

[0333] 13 C-NMR (100 MHz, CDCl3) δ 148.2 (d, 1 J = 288.0 Hz), 147.2 (d, 1 J = 287.3 Hz), 140.83, 140.79, 132.8, 132.7, 128.5, 128.0, 118.4, 118.3, 112.2, 112.1, 53.2 (d, 3 J = 0.8 Hz), 52.7 (d, 3 J = 2.9 Hz), 35.5 (d, 3 J = 1.4 Hz), 34.4 (d, 3 J = 3.6 Hz).

[0334] 19 F-NMR (376 MHz, CDCl3) δ -21.67, -22.62.

[0335] HRMS(ESI) (m / z) calcd for C10H9FN2O [M+Na]+ 215.0591, found 215.0593.

[0337] Example 2-13. Synthesis of Methyl(naphthalen-1-ylmethyl)carbamic fluoride (Formula 1-13)

[0338]

[0339] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 33 mg, 53%.

[0340] Column chromatography (hexane / EtOAc = 10:1)

[0341] 1 H-NMR (400 MHz, CDCl3) δ 8.08-7.85 (m, 3H), 7.60-7.51 (m, 2H), 7.49-7.34 (m, 2H), {4.97

[0342] (s), 4.95 (s), 2H}, {2.94 (s), 2.81 (s), 3H}.

[0343] 13 C-NMR (100 MHz, CDCl3) δ 148.0 (d, 1 J = 287.2 Hz), 147.7 (d, 1 J = 286.6 Hz), 134.0, 133.9, 131.5, 131.1, 130.7, 130.4, 129.3, 129.1, 129.0, 128.9, 127.4 (2C), 127.0, 126.9, 126.24, 126.20, 125.3, 125.2, 123.4, 122.36, 122.35, 51.5 (d, 3 J = 1.1 Hz), 50.7 (d, 3 J = 3.8 Hz), 35.0 (d, 3 J = 1.2 Hz), 33.3 (d, 3 J = 3.8 Hz).

[0344] 19 F-NMR (376MHz, CDCl3) δ -21.22, -22.95.

[0345] HRMS(ESI) (m / z) calcd for C13H12FNO [M+Na]+ 240.0795, found 240.0798.

[0347] Example 2-14. Synthesis of Benzyl(isopropyl)carbamic fluoride (Chemical Formula 1-14)

[0348]

[0349] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 40 mg, 62%.

[0350] Column chromatography (hexane / EtOAc = 10:1)

[0351] 1 H-NMR (400 MHz, CDCl3) δ 7.67-7.63 (m, 3H), 7.42-7.35 (m, 2H), {4.49 (s), 4.43 (s), 2H}, 4.18-4.11 (m, 0.5H), 4.01-3.94 (m, 0.5H), 1.21-1.17 (m, 6H).

[0352] 19 F-NMR (376MHz, CDCl3) δ -15.76, -19.19.

[0354] Example 2-15. Synthesis of Benzyl(phenethyl)carbamic fluoride (Chemical Formula 1-15)

[0355]

[0356] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 34 mg, 62%.

[0357] Column chromatography (hexane / EtOAc = 10:1)

[0358] 1 H-NMR (400 MHz, CDCl3) δ 7.39-7.26 (m, 6H), 7.25-7.12 (m, 4H), {4.38 (s), 4.30 (s), 2H}, {3.49-3.45 (m), 3.41-3.37 (m), 2H}, {2.91-2.87 (m), 2.83-2.79 (m), 2H).

[0359] 13C-NMR (100 MHz, CDCl3) δ 148.30 (d, 1 J = 287.7 Hz), 147.38 (d, 1 J = 289.0 Hz), 138.1, 137.81, 135.75, 135.7, 129.0, 128.9, 128.80, 128.78, 128.73, 128.72, 128.20, 128.16, 127.6 (2C), 126.9, 126.7, 52.0 (d, 3 J = 0.7 Hz), 51.7 (d, 3 J = 3.0 Hz), 49.6, (d, 3 J = 1.5 Hz), 48.6 (d, 3 J = 2.9 Hz), 34.9, 33.5.

[0360] 19 F-NMR (376 MHz, CDCl3) δ -21.56, -21.99.

[0361] HRMS(ESI) (m / z) calcd for C16H16FNO [M+Na]+ 280.1108, found 280.1112.

[0363] Example 2-16. Synthesis of Dibenzylcarbamic fluoride (Formula 1-16)

[0364]

[0365] It was synthesized by method A of Example 1 above, and obtained as a yellow oil with a yield of 50 mg, 81%.

[0366] Column chromatography (hexane / EtOAc = 4:1)

[0367] 1 H-NMR (400 MHz, CDCl3) δ 7.40-7.33 (m, 8H), 7.21-7.20 (m, 2H), 7.20 (m, 2H), 4.43 (s, 2H), 4.35 (s, 2H).

[0368] 19 F-NMR (376MHz, CDCl3) δ -22.66.

[0370] Example 2-17. Synthesis of Allyl(benzyl)carbamic fluoride (Chemical Formula 1-17)

[0371]

[0372] It was synthesized by method A of Example 1 above, and obtained as a colorless oil with a yield of 23 mg, 36%.

[0373] Column chromatography (hexane / EtOAc = 10:1)

[0374] 1 H-NMR (400 MHz, CDCl3) δ 7.39-7.29 (m, 4H), 7.24-7.22 (m, 1H), 5.84-5.68 (m, 1H), 5.29-

[0375] 5.16 (m, 2H), {4.47 (s), 4.42(s), 2H}, {3.86-3.85 (m), 3.77-3.75 (m), 2H}.

[0376] 19 F-NMR (376MHz, CDCl3) δ -22.15, -22.68.

[0378] Example 2-18. Synthesis of Benzyl(prop-2-yn-1-yl)carbamic fluoride (Chemical Formula 1-18)

[0379]

[0380] It was synthesized by method A of Example 1 above, and obtained as a yellow oil with a yield of 26 mg, 40%.

[0381] Column chromatography (hexane / EtOAc = 10:1)

[0382] 1 H-NMR (400 MHz, CDCl3) δ 7.38-7.27 (m, 5H), {4.61 (s), 4.58 (s), 2H}, {4.05 (d, J = 2.5 Hz), 3.94 (d, J = 2.5 Hz), 2H}, 2.35-2.33 (m, 1H).

[0383] 19 F-NMR (376MHz, CDCl3) δ -21.63, -22.38.

[0385] Example 2-19. Synthesis of Methyl(phenyl)carbamic fluoride (Chemical Formula 1-19)

[0386]

[0387] It was synthesized by method B of Example 1 above, and obtained as a yellow oil with a yield of 62 mg, 88%.

[0388] Column chromatography (hexane / EtOAc = 10:1)

[0389] 1 H-NMR (400 MHz, CDCl3) δ 7.42-7.22 (m, 5H), 3.38-3.35 (m, 3H).

[0390] 19 F-NMR (376MHz, CDCl3) δ -15.89, -16.04.

[0392] Example 2-20. Synthesis of 1-(4-Methoxyphenyl)piperazine (Chemical Formula 1-20)

[0393]

[0394] It was synthesized by method B of Example 1 above, and obtained as a white solid with a yield of 10.6 mg, 71%.

[0395] Column chromatography (hexane / EtOAc = 10:1)

[0396] 1 H-NMR (400 MHz, CDCl3) δ 6.91-6.84 (m, 4H), 3.77 (s, 3H), 3.65 (s, 4H), 3.10-3.07 (m, 4H).

[0397] 13 C-NMR (100 MHz, CDCl3) δ 156.4, 146.2 (d, 1 J = 286.5 Hz), 121.3, 119.5 (2C), 116.2, 114.7 (2C), 113.1, 55.6 (2C), 51.3 (d,3 J = 19.8 Hz), 51.0 (d, 3 J = 15.8 Hz), 44.8 (2C).

[0398] 19 F-NMR (376MHz, CDCl3) δ -23.70.

[0399] HRMS(ESI) (m / z) calcd for C12H15FN2O2 [M+Na]+ 239.1190, found 239.1192.

[0401] Example 2-21. Synthesis of 4-(4-(Trifluoromethyl)phenyl)piperazine-1-carbonyl fluoride (Formula 1-21)

[0402]

[0403] It was synthesized by method B of Example 1 above and obtained as a white solid with a yield of 30 mg, 51%.

[0404] Column chromatography (hexane / EtOAc = 10:1)

[0405] 1 H-NMR (400 MHz, CDCl3) δ 7.54-7.52 (m, 2H), 7.00-6.98 (m, 2H), 3.71-3.66 (m, 4H), 3.36-3.30 (m, 4H).

[0406] 13 C-NMR (100 MHz, CDCl3) δ 152.7, 146.2 (d, 1 J = 286.7 Hz), 126.6 (q, 3 J = 3.7 Hz), 124.5 (q, 1 J = 270.8 Hz), 121.9 (q, 2 J = 32.7 Hz), 115.5 (2C), 48.1, 47.9, 44.4 (d, 3 J = 3.6 Hz) (2C).

[0407] 19F-NMR (376MHz, CDCl3) δ -23.70, -61.67.

[0408] HRMS(ESI) (m / z) calcd for C12H12F4N2O [M+Na]+ 299.0778, found 299.0780.

[0410] Example 2-22. Synthesis of (4-Methoxyphenyl)(methyl)carbamic fluoride (Formula 1-22)

[0411]

[0412] It was synthesized by method B of Example 1 above, and obtained as a yellow oil with a yield of 65 mg, 98%.

[0413] Column chromatography (hexane / EtOAc = 10:1)

[0414] 1 H-NMR (400 MHz, CDCl3) δ {7.25 (d, J = 8.3 Hz), 7.14 (d, J = 8.7 Hz), 2H}, 6.92-6.89 (m, 2H), 3.81 (s, 3H), {3.33 (s), 3.31 (s), 3H}.

[0415] 19 F-NMR (376MHz, CDCl3) δ -16.22, 17.47.

[0417] Example 2-23. Synthesis of Benzyl(phenyl)carbamic fluoride (Chemical Formula 1-23)

[0418]

[0419] It was synthesized by method B of Example 1 above and obtained as a white solid with a yield of 53 mg, 86%.

[0420] Column chromatography (hexane / EtOAc = 10:1)

[0421] 1 H-NMR (400 MHz, CDCl3) δ 7.31-7.27 (m, 8H), 7.06-7.05 (m, 2H), 4.83 (s, 2H).

[0422] 19F-NMR (376MHz, CDCl3) δ -14.63, -17.07.

[0424] Example 2-24. Synthesis of Methyl N-benzyl-N-(fluorocarbonyl)-L-alaninate (Formula 1-24)

[0425]

[0426] It was synthesized by method B of Example 1 above, and obtained as a colorless oil with a yield of 30 mg, 51%.

[0427] Column chromatography (hexane / EtOAc = 10:1)

[0428] 1 H-NMR (400 MHz, CDCl3) δ 7.33-7.22 (m, 5H), 3.81 (d, J = 12.8 Hz, 1H), 3.73 (s, 3H), 3.68 (d, J = 12.8 Hz, 1H), 3.40 (q, J = 7.0 Hz, 1H), 1.33 (d, J = 7.0 Hz, 3H).

[0429] 13 C-NMR (100 MHz, CDCl3) δ 170.8 (2C), 148.0 (d, 1 J = 291.0 Hz), 147.3 (d, 1 J = 291.1 Hz), 135.9, 135.7, 128.83, 128.77, 128.1, 128.3, 127.4 (2C), 56.2, 55.7, 52.6, 52.1, 50.81, 50.78, 16.1, 14.8.

[0430] 19 F-NMR (376MHz, CDCl3) δ -17.20,-18.96.

[0431] HRMS(ESI) (m / z) calcd for C12H14FNO3 [M+Na]+ 262.0850, found 262.0852.

[0433] Example 2-25. Synthesis of 4-(Pyridin-3-yl)piperazine-1-carbonyl fluoride (Formula 1-25)

[0434]

[0435] It was synthesized by method B of Example 1 above, and obtained as a colorless oil with a yield of 32 mg, 50%.

[0436] Column chromatography (hexane / EtOAc = 8:1)

[0437] 1 H-NMR (400 MHz, CDCl3) δ 8.21 (ddd, J = 4.95, 1.95, 0.85 Hz, 1H), 7.56-7.52 (m, 1H), 6.72-6.67 (m, 2H), 3.63-3.61 (m, 8H).

[0438] 19 F-NMR (376MHz, CDCl3) δ -23.64.

[0440] Example 2-26. Synthesis of 1,3,4,9-Tetrahydro-2H-pyrido[3,4-b]indole-2-carbonyl fluoride (Formula 1-26)

[0441]

[0442] It was synthesized by method B of Example 1 above, and obtained as a colorless oil with a yield of 13 mg, 21%.

[0443] Column chromatography (hexane / EtOAc = 5:1)

[0444] 1 H-NMR (400 MHz, CDCl3) δ 7.50 (t, J = 6.7 Hz, 1H), 7.34 (dd, J = 8.0, 0.6 Hz, 1H), 7.22 - 7.18 (m, 1H), 7.16 - 7.11 (m, 1H), 4.72 (dt, J = 6.3,1.6 Hz, 2H). 3.84 (dt, J = 19.0, 5.8 Hz, 2H), 2.94 - 2.88 (m, 2H).

[0445] 19 F-NMR (376MHz, CDCl3) δ -19.34, -24.17.

[0447] Foregoing, specific parts of the present invention have been described in detail. It will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the invention. Accordingly, the actual scope of the invention is defined by the appended claims and their equivalents.

[0448] The problem information related to this patent application is as follows.

[0449] Related Research Project: (Applied 2) Research on Ammonia Decomposition-Based Green Hydrogen Extraction Technology

[0450] Research Project ID: GRRC-Hanyang2020 (B02)

[0451] Research Project Name: Gyeonggi Regional Cooperation Research Center Project (GRRC) / Gyeonggi Regional Cooperation Research Center Project (GRRC) / GRRC Basic Project_RCMS

[0452] Supervising Agency: Gyeonggi Provincial Government

Claims

Claim 1 A method for preparing a compound represented by Chemical Formula 1, comprising the step of reacting a compound represented by Chemical Formula 2 below with CF3SO2Na: [Chemical Formula 2] [Chemical Formula 1] In the above Chemical Formulas 1 and 2, R 1 and R 2 Each independently, alkyl group, alkenyl group, alkynyl group, Selected from the group consisting of substituted or unsubstituted benzyl groups, substituted or unsubstituted phenethyl groups and substituted or unsubstituted naphthyl groups, or combined with each other to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl, wherein the substituted benzyl groups, phenethyl groups and naphthyl groups are substituted with alkyl, -CF3, cyano, or alkoxy groups, and the substituted heterocycloalkyl or heteroaryl groups are substituted with alkyl, alkoxy, halogen, substituted or unsubstituted phenyl or pyridyl groups, and the substituted phenyl group is substituted with alkoxy or -CF3. Claim 2 In claim 1, the above R 1 and R 2 The heterocycloalkyl group formed by mutual bonding is any one selected from piperidine, piperazine, and azephan, and the R 1 and R 2 Heteroaryls formed by the bonding of each other or Phosphorus, manufacturing method. Claim 3 A method of preparation according to claim 1, wherein the substituted heterocycloalkyl or heteroaryl is substituted with methyl, methoxy, fluoro, chloro, phenyl, tert-butoxycarbonyl, methoxyphenyl, trifluorophenyl, or pyridyl. Claim 4 In claim 1, the above R 1 and R 2 Each independently, a methyl group, an isopropyl group, an allyl group, , , , , , , , and A manufacturing method, which is one selected from the group consisting of Claim 5 In claim 1, the above [Chemical Formula 1] is any one selected from the group consisting of the following: manufacturing method: [Chemical Formula 1-1] ,[Chemical Formula 1-2] ,[Chemical Formula 1-3] ,[Chemical Formula 1-4] ,[Chemical Formula 1-5] ,[Chemical Formula 1-6] ,[Chemical Formula 1-7] ,[Chemical Formula 1-8] ,[Chemical Formula 1-9] ,[Chemical Formula 1-10] ,[Chemical Formula 1-11] ,[Chemical Formula 1-12] ,[Chemical Formula 1-13] ,[Chemical Formula 1-14] ,[Chemical Formula 1-15] ,[Chemical Formula 1-16] ,[Chemical Formula 1-17] ,[Chemical Formula 1-18] ,[Chemical Formula 1-19] ,[Chemical Formula 1-20] ,[Chemical Formula 1-21] ,[Chemical Formula 1-22] ,[Chemical Formula 1-23] ,[Chemical Formula 1-24] ,[Chemical Formula 1-25] and [Chemical Formula 1-26] . Claim 6 A method of preparation according to any one of claims 1 to 5, wherein the reaction is carried out using DDQ (2,3-Dichloro-5,6-dicyano-1,4-benzoquinone) as a catalyst and under light irradiation conditions. Claim 7 A method of manufacturing, wherein, in any one of claims 1 to 5, the reaction is carried out under an oxygen atmosphere. Claim 8 A method of manufacturing, wherein, in any one of claims 1 to 5, the reaction is carried out in the presence or absence of TFA (Trifluoroacetic acid). Claim 9 delete Claim 10 delete

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