Process for the preparation of n-fluoro-n-alkylsulfonamides

Abstract

The present application relates to a kind of preparation methods of N-fluoro-N-alkyl sulfonamide, specifically, including steps: in the presence of base, in inert solvent, the compound N-alkyl sulfonamide shown in formula II is reacted with the N-fluorobenzene sulfonimidate shown in formula III, and the compound N-fluoro-N-alkyl sulfonamide shown in formula I is formed.

Description

Technical Field

[0001] This invention belongs to the field of organic chemistry, specifically, it relates to a method for synthesizing N-fluoro-N-alkylsulfonamides. Background Technology

[0002] N-fluoro-N-alkylsulfonamides, as shown in Formula I, are widely used as electrophilic fluorinating agents. Recently, it has been found that they can also serve as precursors of nitrogen radicals to participate in hydrogen abstraction reactions of CH bonds, or as amination agents for the efficient synthesis of a series of amine compounds.

[0003] The synthesis of N-fluoro-N-alkylsulfonamides (I) was first reported by Hesse et al., using N-alkylsulfonamides as a starting material and trifluoromethane fluoride (CF3OF) as a fluorinating agent to prepare N-fluoro-N-norbornyl-p-fluorobenzenesulfonamides in a Freon solution with a yield of 71%. This method uses a highly hazardous fluorinating agent and is cumbersome. Barnette et al. used N-alkylbenzenesulfonamides to dehydrogenate under strong base conditions, using 1-5% fluorine gas as a fluorinating agent, in a mixed solvent of trichlorofluoroethane / trichloromethane, and at a low temperature of -78°C, to prepare N-fluoro-N-alkylbenzenesulfonamides in yields of 11-71%, with sulfonyl fluoride and fluorinated amine as byproducts. This method also suffers from high reaction risk, small production scale, and complex purification (J. Am. Chem. Soc. 1984, 106, 452). Meier et al. prepared N-fluoro-N-alkylbenzenesulfonamides in dichloromethane using N-alkylbenzenesulfonamide as a starting material, 6 equivalents of potassium hydride as a base, and 4 equivalents of N-fluorobisbenzenesulfonylimide as a fluorinating agent. Except for the isopropyl base, which had a 95% yield, other substituents such as tert-butyl had only a 55% yield. While the method was relatively mild, the use of a large excess of N-fluorobisbenzenesulfonylimide increased the difficulty of reaction separation (Tetrahedron Lett. 2000, 41, 3291).

[0004] In summary, the current synthesis of N-fluoro-N-alkylsulfonamides in this field suffers from drawbacks such as low reaction yields, poor substrate universality, complex operations, difficult separation, and high costs, which greatly limits their industrial production. Therefore, there is an urgent need in this field to develop an efficient synthetic method for N-fluoro-N-alkylsulfonamides that features mild reaction conditions, simple operation, and good substrate universality. Summary of the Invention

[0005] One object of the present invention is to provide an efficient method for synthesizing N-fluoro-N-alkylsulfonamides that has mild reaction conditions, simple operation, and good substrate versatility.

[0006] A first aspect of the present invention provides a method for preparing N-fluoro-N-alkylsulfonamide, characterized by comprising the steps of:

[0007] In an inert solvent and in the presence of a base, the N-alkylsulfonamide represented by Formula II reacts with the N-fluorobisbenzenesulfonamide represented by Formula III to form the N-fluoro-N-alkylsulfonamide represented by Formula I; wherein the inert solvent is selected from the group consisting of C2-C6 ketone solvents, C2-C6 nitrile solvents, C1-C6 alkane solvents, C2-C6 ester solvents, C2-C8 amide solvents, C2-C8 sulfone solvents, C6-C8 aromatic solvents, or combinations thereof;

[0008]

[0009] In the formula,

[0010] R 1 The substituted or unsubstituted C6-C30 aryl group, or the substituted or unsubstituted 5-30 heteroaryl group; the substitution refers to one or more H groups being substituted by a group selected from the group consisting of: halogen, C6-C30 aryl, C1-C10 alkyl, C3-C8 cycloalkyl, C1-C10 haloalkyl, C1-C10 alkoxy, ester, nitro or cyano;

[0011] R 2 The heterocyclic group is a straight-chain or branched C1-C30 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, or a substituted or unsubstituted 5-12 membered heterocyclic group, wherein the heterocyclic group refers to a heteroatom containing 1-3 heteroatoms each independently selected from N, O or S.

[0012] The amount of N-fluorobisbenzenesulfonamide shown in Formula III is 1 to 5 equivalents of the N-alkylsulfonamide shown in Formula II.

[0013] In another preferred embodiment, R 1 The substituted or unsubstituted C6-C10 aryl group, or the substituted or unsubstituted 5-12 heteroaryl group; the substitution refers to one or more H groups being substituted by a group selected from the group consisting of: halogen, C6-C10 aryl, C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 haloalkyl, C1-C8 alkoxy, ester, nitro or cyano;

[0014] R 2 The heterocyclic group is a straight-chain or branched C1-C12 alkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group, or a substituted or unsubstituted 5-10 membered heterocyclic group, wherein the heterocyclic group contains 1-3 heteroatoms, each independently selected from N, O or S.

[0015] In another preferred embodiment, the compound of formula II is selected from the group consisting of: N-tert-butyl-4-chlorobenzenesulfonamide, N-tert-butyl-3,5-ditrifluoromethylbenzenesulfonamide, N-tert-butylbenzenesulfonamide, N-tert-butyl-3-trifluoromethylbenzenesulfonamide, N-tert-butyl-4-bromobenzenesulfonamide, N-tert-butyl-4-nitrobenzenesulfonamide, N-tert-butyl-4-methoxybenzenesulfonamide, N-tert-butyl-4-tert-butylbenzenesulfonamide, N-tert-butyl-2,5-dimethylbenzenesulfonamide, N-tert-butyl-2,6-difluorobenzenesulfonamide, and N-isopropylbenzenesulfonamide.

[0016] In another preferred embodiment, the base is selected from the group consisting of alkali metal hydrides, alkali metal hydroxides, alkali metal tert-butanol, metal alkylates, or combinations thereof.

[0017] In another preferred embodiment, the alkali is selected from the group consisting of sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, butyllithium, or combinations thereof; preferably sodium hydride.

[0018] In another preferred embodiment, the amount of alkali used is 1 to 10 equivalents of the amount of N-alkylsulfonamide of Formula II; more preferably 1 to 3 equivalents; and even more preferably 2 equivalents.

[0019] In another preferred embodiment, the amount of the N-fluorobisbenzenesulfonamide of Formula III is 1 to 3 equivalents of the N-alkylsulfonamide of Formula II; more preferably 2 equivalents.

[0020] In another preferred embodiment, the inert solvent is selected from the group consisting of C2-C8 amide solvents, C2-C8 sulfone solvents, or combinations thereof.

[0021] In another preferred embodiment, the inert solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or combinations thereof.

[0022] In another preferred embodiment, the C1-C6 alkane solvent does not include dichloromethane.

[0023] In another preferred embodiment, the reaction temperature is -40°C to 50°C; more preferably -10°C to 20°C; and even more preferably -5°C to 5°C.

[0024] In another preferred embodiment, the reaction time is 2 to 40 hours; more preferably 3 to 10 hours.

[0025] In another preferred embodiment, the reaction is carried out under an inert atmosphere, which is nitrogen or argon.

[0026] In another preferred embodiment, the method includes the steps of reacting at -10°C to 10°C for 1-3 hours, and then reacting at room temperature for 1-3 hours.

[0027] In another preferred embodiment, the method further includes separation and purification.

[0028] In another preferred embodiment, the separation and purification includes: pouring into ice water, extracting with an inert solvent, drying and concentrating, and performing column chromatography or recrystallization.

[0029] In a second aspect of the invention, an N-fluoro-N-alkylsulfonamide is provided, said N-fluoro-N-alkylsulfonamide being prepared using the method described in the first aspect of the invention.

[0030] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Detailed Implementation

[0031] Through extensive and in-depth research and numerous experiments, the inventors have developed for the first time a highly efficient synthetic method for N-fluoro-N-alkylsulfonamides, characterized by mild reaction conditions, simple operation, and broad substrate applicability. The method involves reacting N-fluorobisbenzenesulfonamides with various N-alkylsulfonamides to obtain N-fluoro-N-alkylsulfonamides in high yield. Based on this, the inventors completed this invention.

[0032] the term

[0033] Unless otherwise specified herein, all terms and abbreviations shall have their conventional meanings as are known to those skilled in the art.

[0034] The term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0035] As used herein, “N-fluorobis(benzenesulfonyl)imide” or “NFSI” are used interchangeably and both refer to the compound shown in Formula III below:

[0036]

[0037] Preparation method of N-fluoro-N-alkylsulfonamide

[0038] The purpose of this invention is to provide a method for preparing N-fluoro-N-alkylsulfonamides that has mild reaction conditions, simple operation, and good substrate universality.

[0039] This N-fluoro-N-alkylsulfonamide can be prepared by the following method; however, the conditions of this method, such as reactants, solvent, base, amount of compound used, reaction temperature, and reaction time, are not limited to those explained below.

[0040] Typically, the preparation method provided by the present invention includes the following steps:

[0041] In an inert solvent and in the presence of a base, the N-alkylsulfonamide of Formula II reacts with the N-fluorobisbenzenesulfonamide of Formula III to form the N-fluoro-N-alkylsulfonamide of Formula I.

[0042]

[0043] In this step, the base used in the reaction is a base commonly used in the art, including, but not limited to, alkali metal hydrides, alkali metal hydroxides, alkali metal tert-butanol, metal alkylates, or combinations thereof; preferably, the base is selected from the group consisting of: sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, butyllithium, or combinations thereof; more preferably, sodium hydride.

[0044] In this step, there are no particular limitations on the proportions of the reactants. For example, the amount of base used is 1 to 10 equivalents of the N-alkylsulfonamide of Formula II; preferably 1 to 3 equivalents; more preferably 2 equivalents. The amount of N-fluorobisbenzenesulfonamide of Formula III used is 1 to 5 equivalents of the N-alkylsulfonamide of Formula II; preferably 1 to 3 equivalents; more preferably 2 equivalents.

[0045] The reaction solvent, reaction temperature, and reaction time can be selected according to the specific reactants. For example, the inert solvent is selected from the group consisting of C2-C6 ketone solvents, C2-C6 nitrile solvents, C1-C6 alkane solvents, C2-C6 ester solvents, C2-C8 amide solvents, C2-C8 sulfone solvents, and C6-C8 aromatic solvents, or combinations thereof. Preferably, the inert solvent is selected from the group consisting of acetonitrile, acetone, chloroform, ethyl acetate, toluene, nitrobenzene, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or combinations thereof; more preferably, it is N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or combinations thereof. The reaction temperature is -40℃ to 50℃; more preferably -10℃ to 20℃; more preferably -5℃ to 5℃. The reaction time is 2 to 40 hours; more preferably 3 to 10 hours.

[0046] In one specific embodiment, the reaction is carried out under an inert atmosphere, which is nitrogen or argon.

[0047] In one specific embodiment, the method further includes separation and purification. The separation and purification includes: pouring the reaction system obtained from the reaction into ice water, extracting with the aforementioned inert solvent, drying and concentrating, and then performing column chromatography or recrystallization to obtain the N-fluoro-N-alkylsulfonamide.

[0048] Compared with the prior art, the main advantages of the present invention include:

[0049] (a) The preparation method of the present invention has a high yield, which can reach more than 80%.

[0050] (b) The reaction conditions are mild, the operation is simple, and the substrate is universal.

[0051] (c) Low amounts of alkali and fluorinating reagents are used, and post-processing purification is simple.

[0052] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0053] Example 1

[0054] Add NaH (4.24 g, 106 mmol, 60 wt% dispersed in solid paraffin) to a 500 mL round-bottom flask, then add DMF (200 mL). Dissolve N-tert-butyl-4-chlorobenzenesulfonamide (13.0 g, 53 mmol) in DMF (50 mL) and add it to the above reaction solution at 0 °C. After stirring for 30 minutes, slowly add N-fluorobisbenzenesulfonylimide NFSI (33.4 g, 106 mmol). After reacting at 0 °C for 2 hours, continue the reaction at room temperature for another 2 hours.

[0055] The reaction solution was quenched in ice water, and extracted with dichloromethane (100 mL * 3). The combined organic phases were washed with water (200 mL * 3) several times, dried over anhydrous magnesium sulfate, filtered, evaporated to dryness, and then subjected to column chromatography (petroleum ether: ethyl acetate = 50: 1) to give a white solid product. The product was then recrystallized in petroleum ether to give the final product (12.3 g, yield 88%).

[0056] 1 H NMR (400MHz, CDCl3) δ7.92 (d, J = 8.8Hz, 2H), 7.54 (d, J = 8.4Hz, 2H), 1.48 (d, J = 0.4Hz, 9H); 13 C NMR (100MHz, CDCl3) δ141.0, 135.7, 130.4, 129.3, 66.8 (d, J = 12.2Hz), 27.1 (d, J = 6.1Hz); 19 F NMR(376MHz,CDCl3)δ-61.92(s).HRMS:m / z(EI)calculated[M] + :265.0340,measured:265.0342.

[0057] Example 2

[0058] Add NaH (4.72 g, 118 mmol, 60 wt% dispersed in solid paraffin) to a 500 mL round-bottom flask, then add DMF (250 mL). Dissolve N-tert-butyl-3,5-bis(trifluoromethyl)benzenesulfonamide (24.2 g, 59 mmol) in DMF (50 mL) and add it to the above reaction solution at 0 °C. After stirring for 30 minutes, slowly add NFSI (37.2 g, 118 mmol). After reacting at 0 °C for 2 hours, continue the reaction at room temperature for 2 hours.

[0059] The reaction solution was quenched in ice water, and extracted with dichloromethane (100 mL * 3). The combined organic phases were washed with water (200 mL * 3) several times, dried over anhydrous magnesium sulfate, filtered, evaporated to dryness, and then subjected to column chromatography (petroleum ether: ethyl acetate = 50: 1) to give a white solid product. The product was then recrystallized in petroleum ether to give the final product (20.5 g, yield 81%).

[0060] 1 13C NMR (100MHz, CDCl3) δ140.91, 140.89, 139.5, 132.8 (t, J = 34.3Hz), 129.1 (d, J = 3.1Hz), 128. 3,127.5(t,J=3.3Hz), 126.1,122.3(t,J=271.4Hz), 70.4(d,J=12.0Hz), 26.8(d,J=5.9Hz); 19 F NMR(376MHz, CDCl3)δ-60.48(s),-63.00(s).

[0061] Example 3

[0062] The procedure was the same as in Example 1, except that the raw material was replaced with N-tert-butylbenzenesulfonamide (7.64 g, 36 mmol), and the reaction yielded a colorless liquid (7.79 g, 94% yield). 1 H NMR (400MHz, CDCl3) δ7.98 (d, J = 7.6Hz, 2H), 7.66 (t, J = 7.6Hz, 1H), 7.55 (t, J = 8.0Hz, 2H), 1.47 (d, J = 1.2Hz, 9H); 13C NMR (100MHz, CDCl3) δ137.3, 134.2, 129.0 (d, J = 1.6Hz), 128.9, 66.6 (d, J = 11.4Hz); 27.2 (d, J = 6.0Hz); 19 F NMR(376MHz, CDCl3)δ-62.40(s).

[0063] Example 4

[0064] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-3-trifluoromethylbenzenesulfonamide (4.7 g, 17 mmol), and the reaction yielded a white solid (4.06 g, yield 81%). 1 H NMR (400MHz, CDCl3) δ8.24(s,1H),8.17(d,J=8.0Hz,1H),7.93(d,J=8.0Hz,1H),7.72(t,J=8.0Hz),1.51(d,J=1.6Hz,9H); 13 C NMR (100MHz, CDCl3) δ138.7(q,J=5.5Hz),132.3,131.9(q,J=33.7Hz),130.8(q,J=3.7Hz) ,129.8,126.2(q,J=4.0Hz),123.1(q,J=271.9Hz),67.2(d,J=12.1Hz); 27.2(d,J=6.1Hz); 19 FNMR(376MHz, CDCl3)δ-61.47(s),-62.91(s).

[0065] Example 5

[0066] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-4-bromobenzenesulfonamide (5.1 g, 17.5 mmol), and the reaction yielded a white solid (5.37 g, 99% yield). 1 H NMR (400MHz, CDCl3) δ7.83 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 8.8 Hz, 2H), 1.47 (d, J = 1.6 Hz, 9H); 13 C NMR (100MHz, CDCl3) δ136.3, 132.3, 130.5, 129.6, 66.8 (d, J = 12.2Hz), 27.2 (d, J = 6.1Hz); 19 F NMR(376MHz, CDCl3)δ-61.81(s).

[0067] Example 6

[0068] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-4-nitrobenzenesulfonamide (4.7 g, 18 mmol), and the reaction yielded a white solid (4.1 g, yield 81%). 1 H NMR (400MHz, CDCl3) δ8.40(d,J=8.4Hz,2H),8.17(d,J=8.4Hz,2H),1.51(d,J=1.6Hz,9H); 13 C NMR (100MHz, CDCl3) δ150.9, 142.7, 130.4, 124.1, 67.4 (d, J = 12.3Hz); 27.2 (d, J = 5.9Hz); 19 F NMR(376MHz, CDCl3)δ-61.15(s).

[0069] Example 7

[0070] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-4-methoxybenzenesulfonamide (4.1 g, 17 mmol), and the reaction yielded a white solid (3.67 g, yield 83%). 1 H NMR (400MHz, CDCl3) δ7.90 (d, J = 8.8Hz, 2H), 7.01 (d, J = 8.8Hz, 2H), 3.89 (s, 3H), 1.45 (d, J = 1.2Hz, 9H); 13 C NMR (100MHz, CDCl3) δ164.1, 131.2, 128.5, 114.1, 66.2 (d, J = 12.5Hz), 55.6, 27.0 (d, J = 6.0Hz); 19 F NMR(376MHz, CDCl3)δ-62.30(s).

[0071] Example 8

[0072] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-4-tert-butylbenzenesulfonamide (3.0 g, 11 mmol), and the reaction yielded a white solid (2.85 g, yield 89%). 1 H NMR (400MHz, CDCl3) δ7.89 (d, J = 8.4Hz, 2H), 7.56 (d, J = 8.4Hz, 2H), 1.47 (d, J = 1.2Hz, 9H), 1.35 (s, 9H); 13 C NMR (100MHz, CDCl3) δ158.3, 134.3, 128.9 (d, J = 1.0Hz), 126.0, 66.5 (d, J = 11.9Hz), 35.3, 31.0, 27.2 (d, J = 6.1Hz); 19F NMR(376MHz, CDCl3)δ-62.39(s).

[0073] Example 9

[0074] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-2,5-dimethylbenzenesulfonamide (4.67 g, 19 mmol), and the reaction yielded a colorless liquid (4.43 g, yield 84%). 1 H NMR (400MHz, CDCl3) δ7.85 (s, 1H), 7.32 (d, J = 7.6Hz, 1H), 7.21 (d, J = 8.0Hz, 1H), 2.65 (s, 3H), 2.38 (s, 3H), 1.54 (d, J = 1.2Hz, 9H); 13 CNMR (100MHz, CDCl3) δ136.0, 135.9, 134.9, 134.8, 132.4, 131.3, 66.4 (d, J = 12.0Hz), 27.2 (d, J = 6.2Hz), 20.4, 19.7; 19 F NMR(376MHz, CDCl3)δ-61.92(s).

[0075] Example 10

[0076] The procedure was the same as in Example 1, except that the starting material was replaced with N-tert-butyl-2,6-difluorobenzenesulfonamide (4.30 g, 17 mmol), and the reaction yielded a white solid (3.97 g, yield 86%). 1 H NMR (400MHz, CDCl3) δ7.64-7.59 (m, 1H), 7.05 (t, J = 8.4Hz, 2H), 1.53 (d, J = 1.6Hz, 9H); 13 C NMR (100MHz, CDCl3) δ160.4 (dd, J = 262.6, 3.3Hz), 136.8 (t, J = 11.6Hz), 115.0 (t, J = 14.4Hz), 126.0, 67.3 (d, J = 12.2Hz), 27.0 (d, J = 6.2Hz); 19 F NMR(376MHz, CDCl3)δ-61.70(s),-104.31-104.36(m).

[0077] Example 11

[0078] The procedure was the same as in Example 1, except that the starting material was replaced with N-isopropylbenzenesulfonamide (6.00 g, 30 mmol), and the reaction yielded a white solid (5.47 g, yield 84%). 1H NMR (400MHz, CDCl3) δ7.98(d,J=7.6Hz,2H),7.71(t,J=8.0Hz,1H),7.59(t,J=8.0Hz,2H),4.25–4.01(m,1H),1.33(d,J=6.4Hz,6H). 13 C NMR (100MHz, CDCl3) δ135.2, 134.5, 129.3 (d, J = 1.2Hz), 129.2, 55.4 (d, J = 13.9Hz), 19.3 (d, J = 6.1Hz). 19 F NMR (376MHz, CDCl3) δ-76.08 (d, J=34.6Hz).

[0079] Comparative Example 12

[0080] The procedure was performed as described in Example 1, with 13.0 g of N-tert-butyl-4-chlorobenzenesulfonamide used as the raw material. The reaction yielded a white solid (12.3 g, yield 88%).

[0081] Following the reaction conditions described in Nature 2019, 574, 516, NaH (3.6 g, 60 mmol, 60 wt% dispersed in solid paraffin) was added to a 500 mL round-bottom flask, followed by 250 mL of dichloromethane. N-tert-butyl-4-chlorobenzenesulfonamide (7.43 g, 30 mmol) was dissolved in 50 mL of dichloromethane and slowly added dropwise to the above reaction solution under nitrogen protection at room temperature. After stirring for 30 minutes, NFSI (37.3 g, 120 mmol) was slowly added, and the reaction was continued with stirring at room temperature for 6 hours.

[0082] The reaction solution was quenched with water, extracted with dichloromethane (200 mL * 3), dried over anhydrous magnesium sulfate, filtered, and then subjected to column chromatography (petroleum ether: ethyl acetate = 20: 1) to obtain a white solid product. The product was then recrystallized in petroleum ether to obtain the final product (4.07 g, yield 51%).

[0083]

[0084] It can be seen that the present invention significantly improves the synthesis yield of N-fluoroN-tert-butyl-4-chlorobenzenesulfonamide, and greatly reduces the amount of fluorinating reagent used, making the post-processing and separation of the reaction more convenient.

[0085] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for preparing N-fluoro-N-alkylsulfonamide, characterized in that, Including the following steps: In an inert solvent and in the presence of a base, the N-alkylsulfonamide of Formula II reacts with the N-fluorobisbenzenesulfonamide of Formula III to form the N-fluoro-N-alkylsulfonamide of Formula I; wherein the inert solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, or combinations thereof. In the formula, R 1 The substituted or unsubstituted C6-C10 aryl group; the substitution means that one or more H are substituted by a group selected from the group consisting of: halogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, nitro or cyano; R 2 It is tert-butyl or isopropyl; The amount of N-fluorobisbenzenesulfonamide shown in Formula III is 1 to 3 equivalents of the N-alkylsulfonamide shown in Formula II. The alkali mentioned is NaH; The amount of alkali used is 1 to 3 equivalents of the amount of N-alkylsulfonamide used in Formula II.

2. The method as described in claim 1, characterized in that, The compound of formula II is selected from the group consisting of: N-tert-butyl-4-chlorobenzenesulfonamide, N-tert-butyl-3,5-ditrifluoromethylbenzenesulfonamide, N-tert-butylbenzenesulfonamide, N-tert-butyl-3-trifluoromethylbenzenesulfonamide, N-tert-butyl-4-bromobenzenesulfonamide, N-tert-butyl-4-nitrobenzenesulfonamide, N-tert-butyl-4-methoxybenzenesulfonamide, N-tert-butyl-4-tert-butylbenzenesulfonamide, N-tert-butyl-2,5-dimethylbenzenesulfonamide, N-tert-butyl-2,6-difluorobenzenesulfonamide, and N-isopropylbenzenesulfonamide.

3. The method as described in claim 1, characterized in that, The amount of N-fluorobisbenzenesulfonamide shown in Formula III is 2 equivalents of the N-alkylsulfonamide shown in Formula II.

4. The method as described in claim 1, characterized in that, The reaction temperature is -40℃ to 50℃.

5. The method as described in claim 1, characterized in that, The reaction temperature is -10℃ to 20℃.

6. The method as described in claim 1, characterized in that, The reaction temperature is -5 to -5℃.

7. The method as described in claim 1, characterized in that, The reaction time is 2 to 40 hours.

8. The method as described in claim 1, characterized in that, The method also includes separation and purification.

9. The method as described in claim 8, characterized in that, The separation and purification process includes: pouring into ice water, extracting with an inert solvent, drying and concentrating, and then performing column chromatography or recrystallization.

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