Beta-trifluoromethyl unsaturated amides and methods for their synthesis

Abstract

The application belongs to the technical field of medicine preparation, and particularly relates to a beta-trifluoromethyl unsaturated amide and a synthesis method thereof. The synthesis method is that aromatic amine, a palladium catalyst, a phosphorus ligand, a base, a solvent and 1-chloro-3,3,3-trifluoropropene are put into an autoclave for reaction, carbon monoxide is introduced into the autoclave, and heating is performed for reaction; after the reaction is completed, the introduction of carbon monoxide is stopped, dichloromethane is added to dilute the reaction liquid, the organic solvent is removed by rotary evaporation, and the remaining product is separated and purified by silica gel column chromatography to obtain the beta-trifluoromethyl unsaturated amide. The method is simple in operation, low in reaction energy consumption, small in synthesis cost, friendly in technical environment, and expected to be applied to the fields of organic synthesis and medicinal chemistry containing unsaturated amide.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a β-trifluoromethyl unsaturated amide and its synthesis method. Background Technology

[0002] Aromatic amines are extremely important organic raw materials, widely used in the production of dyes, pharmaceuticals, agrochemicals, additives, surfactants, textile auxiliaries, chelating agents, polymers, and flame retardants. Aromatic amines are crucial intermediates in organic synthesis, and with the rapid development of my country's industry and economy, the demand for aromatic amines from various related industries will continue to grow.

[0003] Trifluoromethyl groups possess strong electron-withdrawing and lipophilic properties, and their CF bonds are highly stable. Introducing trifluoromethyl groups into the molecular structure can significantly alter the acidity, polarity, lipophilicity, and chemical and biological activities of compounds. Compounds containing trifluoromethyl groups play a crucial role in pharmaceuticals, pesticides, dyes, and materials. Examples include the anticancer drug sorafenib, the antidepressant fluoxetine, the novel broad-spectrum fungicide oxime ester for crop protection, and ZLI-2857, a typical material for liquid crystal displays.

[0004] β-Trifluoromethyl unsaturated amides are a novel class of amide compounds. Due to the low reactivity of the trifluoromethyl group, the synthesis of these compounds has long been impossible. This has severely limited the application of these important amide compounds in medicinal chemistry research, making the design and synthesis of these compounds extremely urgent. Summary of the Invention

[0005] The purpose of this invention is to provide a β-trifluoromethyl unsaturated amide and its synthesis method, which solves the problem of low synthesis efficiency of unsaturated amide compounds in the prior art.

[0006] A β-trifluoromethyl unsaturated amide, the structure of which is shown below:

[0007]

[0008] Wherein, R is selected from phenyl, substituted phenyl,

[0009] The substituents of the substituted phenyl group are selected from any one or more of alkoxy groups with 1-8 carbon atoms, alkyl groups with 1-8 carbon atoms, halogen groups, or nitro groups.

[0010] The above-mentioned method for synthesizing β-trifluoromethyl unsaturated amides includes the following steps:

[0011] (1) Aromatic amine, palladium catalyst, phosphorus ligand, base, solvent and 1-chloro-3,3,3-trifluoropropene are placed in a high-pressure reactor for reaction, and carbon monoxide is introduced into the high-pressure reactor and heated for reaction;

[0012] (2) After the reaction was complete, the carbon monoxide was stopped, dichloromethane was added to dilute the reaction solution, the organic solvent was removed by rotary evaporation, and the remaining product was separated and purified by silica gel column chromatography to obtain β-trifluoromethyl unsaturated amide.

[0013] Furthermore, in step (1), the aromatic amine is aniline, substituted aniline, or...

[0014] The substituents of substituted aniline are selected from any one or more of alkoxy groups having 1-8 carbon atoms, alkyl groups having 1-8 carbon atoms, halogen groups, or nitro groups.

[0015] Furthermore, in step (1), the palladium catalyst is any one of palladium acetate, bis(triphenylphosphine) palladium chloride, bis(cyanobenzene) palladium dichloride, bisacetonitrile palladium chloride, tetra(triphenylphosphine) palladium, bis(dibenzylideneacetone) palladium, or allyl palladium(II) chloride dimer.

[0016] Further, in step (1), the phosphorus ligand is any one of 2-bicyclohexylphosphine-2',6'-diisopropoxybiphenyl, tritert-tert-butylphosphine tetrafluoroborate, 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene, 2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl, 1,1'-binaphthyl-2,2'-bis(diphenylphosphine), tri(2-furanyl)phosphine, or 2-dicyclohexylphosphine-2'-methylbiphenyl.

[0017] Further, in step (1), the base is any one of potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, triethylamine, cesium acetate, 1,8-diazabicycloundecane, N-ethyldiisopropylamine, 4-dimethylaminopyridine, or N,N-diethylaniline.

[0018] Furthermore, in step (1), the solvent is any one of tetrahydrofuran, toluene, 1,4-dioxane, acetonitrile, 1,2-dichloroethane, N,N-dimethylformamide, trifluorotoluene, chlorobenzene, or n-heptane.

[0019] Furthermore, in step (1), the pressure of carbon monoxide is 10 atm, the reaction time is 12 h, and the reaction temperature is 80-100 °C; the mass ratio of aromatic amine, palladium catalyst, phosphorus ligand, base, solvent and 1-chloro-3,3,3-trifluoropropene is 1:0.03:0.05:2:2:2.

[0020] Furthermore, in step (2), the chromatographic separation uses a 200-300 mesh silica gel column.

[0021] Furthermore, in step (2), the eluent used during chromatographic separation is a mixture of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of (10-6):1.

[0022] The reaction equation for the synthesis method of the β-trifluoromethyl unsaturated amide described in this invention is as follows:

[0023]

[0024] The beneficial effects of this invention are:

[0025] The present invention provides a one-step method for the direct preparation of β-trifluoromethyl unsaturated amides. This method is simple to operate, has low reaction energy consumption, low synthesis cost, and is environmentally friendly. It is expected to be applied in the fields of organic synthesis and medicinal chemistry for the synthesis of unsaturated amides. Detailed Implementation

[0026] The present invention will be further described in conjunction with the embodiments.

[0027] The method for synthesizing β-trifluoromethyl unsaturated amide according to the present invention includes the following steps:

[0028] (1) Aromatic amine, palladium catalyst, phosphorus ligand, base, solvent and 1-chloro-3,3,3-trifluoropropene are placed in a high-pressure reactor for reaction, and carbon monoxide is introduced into the high-pressure reactor and heated for reaction;

[0029] (2) After the reaction was complete, the carbon monoxide was stopped, dichloromethane was added to dilute the reaction solution, the organic solvent was removed by rotary evaporation, and the remaining product was separated and purified by silica gel column chromatography to obtain β-trifluoromethyl unsaturated amide.

[0030] The following examples all follow a feeding ratio of 1:0.03:0.05:2:2:2 based on the mass ratio of aromatic amine, palladium catalyst, phosphorus ligand, alkali, solvent and 1-chloro-3,3,3-trifluoropropylene.

[0031] Example 1

[0032] This invention discloses a method for the palladium-catalyzed carbonylation synthesis of β-trifluoromethyl unsaturated amides, which is implemented according to the following steps:

[0033] p-Methoxyaniline, allyl palladium(II) chloride dimer, 2-bicyclohexylphosphine-2',6'-diisopropoxybiphenyl, triethylamine, acetonitrile, and 1-chloro-3,3,3-trifluoropropene were added and placed in an autoclave for reaction. Carbon monoxide was introduced into the autoclave at 10 atm, and the reaction time was 12 h at 100 °C. After the reaction was completed, dichloromethane was added to dilute the reaction solution, and the organic solvent was removed by rotary evaporation. The remaining product was then purified by separation and purification using a 200-300 mesh silica gel column to obtain (E)-4,4,4-trifluoro-N-(4-methoxyphenyl)but-2-enamide.

[0034] During chromatographic separation, a mixture of petroleum ether and ethyl acetate was used as the eluent, with a petroleum ether:ethyl acetate ratio of 8:1; the data are as follows:

[0035] 1 H NMR (400MHz, CDCl3) δ7.51 (s, 1H), 7.46 (d, 2H, J = 9.0Hz), 6.88 (d, 2H, J = 9.0Hz), 6.83 (t, 1H, J = 6.7, 6.7Hz), 6.62 (dd, 1H, J = 15.3, 2.0Hz), 3.80 (s, 3H);

[0036] 13 C NMR (101MHz, CDCl3) δ160.20,157.09,131.04,129.84,129.23,128.88,128.53,123.69,121.95,114.23,55.39;

[0037] 19 F NMR (376MHz, CDCl3) δ-65.10 (s, 3F);

[0038] HRMS(ESI)m / z:[M+Na] + calcd.for C 11 H 10 F3NNaO2 268.0664; found:268.0555.

[0039] Example 2

[0040] This invention discloses a method for the palladium-catalyzed carbonylation synthesis of β-trifluoromethyl unsaturated amides, which is implemented according to the following steps:

[0041] p-Ethylaniline, palladium acetate, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, potassium carbonate, tetrahydrofuran, and 1-chloro-3,3,3-trifluoropropene were added and placed in an autoclave for reaction. Carbon monoxide was introduced into the autoclave at 10 atm, and the reaction time was 12 h at 100 °C. After the reaction was completed, dichloromethane was added to dilute the reaction solution, and the organic solvent was removed by rotary evaporation. The remaining product was then purified by separation using a 200-300 mesh silica gel column to obtain (E)-N-(4-ethylphenyl)-4,4-4-trifluorobut-2-eneamide.

[0042] During chromatographic separation, a mixture of petroleum ether and ethyl acetate was used as the eluent, with a petroleum ether:ethyl acetate ratio of 10:1; the data are as follows:

[0043] 1 H NMR (400MHz, CDCl3) δ7.64 (s, 1H), 7.46 (dd, 2H, J = 8.4Hz), 7.17 (dd, 2H, J = 8.4Hz), 6 .85(m,1H),6.64(m,1H),2.63(q,2H,J=7.7,7.6,7.6Hz),1.22(t,3H,J=7.6,7.6Hz);

[0044] 13 C NMR (101MHz, CDCl3) δ162.86,142.34,129.99,128.90,128.63,128.57,128.39,127.02,123.85,121.17,37.72;

[0045] 19 F NMR (376MHz, CDCl3) δ-65.00 (s, 3F);

[0046] HRMS(ESI)m / z:[M+Na] + calcd.for C 12 H 12 F3NNaO 266.0871; found:266.0762.

[0047] Example 3

[0048] This invention discloses a method for the palladium-catalyzed carbonylation synthesis of β-trifluoromethyl unsaturated amides, which is implemented according to the following steps:

[0049] p-Ethoxyaniline, palladium di(cyanophenyl) dichloride, tritert-tert-butylphosphine tetrafluoroborate, sodium carbonate, toluene, and 1-chloro-3,3,3-trifluoropropene were added and placed in an autoclave for reaction. Carbon monoxide was introduced into the autoclave at 10 atm, and the reaction time was 12 h at 100 °C. After the reaction was completed, dichloromethane was added to dilute the reaction solution, and the organic solvent was removed by rotary evaporation. The remaining product was then purified by separation and purification using a 200-300 mesh silica gel column to obtain (E)-N-(4-ethoxyphenyl)-4,4-4-trifluorobut-2-eneamide.

[0050] During chromatographic separation, a mixture of petroleum ether and ethyl acetate was used as the eluent, with a petroleum ether:ethyl acetate ratio of 9:1; the data are as follows:

[0051] 1 H NMR (400MHz, CDCl3) δ11.61 (s, 1H), 7.60 (s, 1H), 7.46 (d, 2H, J = 8.9Hz), 6.98–6.78 (m, 2 H), 6.64 (dd, 1H, J = 15.3, 2.0Hz), 4.00 (t, 2H, J = 7.0, 7.0Hz), 1.41 (d, 3H, J = 7.0, 7.0Hz);

[0052] 13 C NMR (101MHz, CDCl3) δ160.29,156.54,131.18,129.88,129.23,128.88,122.00,114.90,63.72,14.79;

[0053] 19 F NMR (376MHz, CDCl3) δ-65.11 (s, 3F);

[0054] HRMS(ESI)m / z:[M+Na] + calcd.for C 12 H 12 F3NNaO2 282.0820; found:282.0711.

[0055] Example 4

[0056] This invention discloses a method for the palladium-catalyzed carbonylation synthesis of β-trifluoromethyl unsaturated amides, which is implemented according to the following steps:

[0057] p-Nitroaniline, bis(triphenylphosphine)palladium chloride, 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene, 1,8-diazabicycloundecane, 1,4-dioxane, and 1-chloro-3,3,3-trifluoropropene were added and placed in an autoclave for reaction. Carbon monoxide was introduced into the autoclave at 10 atm, and the reaction time was 12 h at 80 °C. After the reaction was completed, dichloromethane was added to dilute the reaction solution, and the organic solvent was removed by rotary evaporation. The remaining product was then purified by separation using a 200-300 mesh silica gel column to obtain (E)-4,4,4-trifluoro-N-(4-nitrophenyl)but-2-enamide.

[0058] During chromatographic separation, a mixture of petroleum ether and ethyl acetate was used as the eluent, with a petroleum ether:ethyl acetate ratio of 8:1; the data are as follows:

[0059] 1 H NMR (400MHz, d6-acetone) δ10.25 (s, 1H), 8.27 (d, 2H, J = 9.3Hz), 7.99 (d, 2H, J = 9.3Hz), 7.00 (d, 2H, J = 2.0Hz);

[0060] 13 C NMR (101MHz, d6-acetone) δ205.39,161.07,144.30,143.70,132.27,132.21,132.15,132.09,128.83,128.49,128.14,127.80,124.80,119.40;

[0061] 19 F NMR(376MHz,d6-acetone)δ-65.73(s,3F);

[0062] HRMS(ESI)m / z:[M+Na] + calcd.for C 10 H7F3N2NaO3 283.0409; found:283.0392.

[0063] Example 5

[0064] This invention discloses a method for the palladium-catalyzed carbonylation synthesis of β-trifluoromethyl unsaturated amides, which is implemented according to the following steps:

[0065] m-methylaniline, palladium chloride diacetonitrile, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, N,N-diethylaniline, 1,2-dichloroethane, and 1-chloro-3,3,3-trifluoropropene were added and placed in an autoclave for reaction. Carbon monoxide was introduced into the autoclave at 10 atm, and the reaction time was 12 h at 90 °C. After the reaction was completed, dichloromethane was added to dilute the reaction solution, and the organic solvent was removed by rotary evaporation. The remaining product was then purified by separation using a 200-300 mesh silica gel column to obtain (E)-4,4,4-trifluoro-N-(m-tolyl)but-2-eneamide.

[0066] During chromatographic separation, a mixture of petroleum ether and ethyl acetate was used as the eluent, with a petroleum ether:ethyl acetate ratio of 6:1; the data are as follows:

[0067] 1 H NMR (400MHz, CDCl3) δ7.75 (s, 1H), 7.40 (s, 1H), 7.33 (d, 1H, J = 8.1Hz), 7.23 (t, 1 H, J=16.2, 8.5Hz), 6.98 (d, 1H, J=7.6Hz), 6.85 (s, 1H), 6.65 (s, 1H), 2.32 (s, 3H);

[0068] 13 C NMR (101MHz, CDCl3) δ160.49,139.25,136.81,131.21,131.15,129.56,129.21,129.03,126.29,123.75,121.07,120.94,117.40,21.44;

[0069] 19 F NMR(376MHz, CDCl3)δ-65.03.(s,3F);

[0070] HRMS(ESI)m / z:[M+Na] + calcd.for C 11 H 10 F3NNaO 252.0714; found:252.0604.

[0071] Example 6

[0072] This invention discloses a method for the palladium-catalyzed carbonylation synthesis of β-trifluoromethyl unsaturated amides, which is implemented according to the following steps:

[0073] o-Methoxyaniline, bis(dibenzylacetone)palladium, tris(2-furanyl)phosphine, cesium carbonate, N,N-dimethylformamide, and 1-chloro-3,3,3-trifluoropropene were added and reacted in an autoclave. Carbon monoxide was introduced into the autoclave at 10 atm, the reaction time was 12 h, and the reaction temperature was 80 °C. After the reaction was completed, dichloromethane was added to dilute the reaction solution, the organic solvent was removed by rotary evaporation, and the remaining product was purified by separation and purification using a 200-300 mesh silica gel column to obtain (E)-4,4,4-trifluoro-N-(2-methoxyphenyl)but-2-eneamide.

[0074] During chromatographic separation, a mixture of petroleum ether and ethyl acetate was used as the eluent, with a petroleum ether:ethyl acetate ratio of 10:1; the data are as follows:

[0075] 1 H NMR (400MHz, CDCl3) δ8.43 (d, 1H, J = 8.1Hz), 8.05 (s, 1H), 7.11 (t, 1H, J = 7.9H z),6.99(t,1H,J=8.5Hz),6.95–6.78(m,2H),6.74–6.60(m,1H),3.91(s,3H);

[0076] 13 C NMR (101MHz, CDCl3) δ160.06,148.03,131.55,131.49,129.23,128.88,126.82,124.89,123.87,121.20,120.19,110.02,55.73;

[0077] 19 F NMR (376MHz, CDCl3) δ-64.79 (s, 3F);

[0078] HRMS(ESI)m / z:[M+Na] + calcd.for C 11 H 10 F3NNaO2 268.0664; found:268.0554.

[0079] Example 7

[0080] The synthesis method of Example 7 is the same as that of Example 1, except that the substrate structure is: The palladium catalyst is tetra(triphenylphosphine)palladium, the phosphorus ligand is 2-dicyclohexylphosphine-2'-methylbiphenyl, the base is sodium hydroxide, and the solvent is trifluorotoluene, resulting in different product structures. The product structure is as follows: See Table 1 for details.

[0081] Example 8

[0082] The synthesis method of Example 8 is the same as that of Example 1, except that the substrate structure is: The use of cesium acetate as the base and chlorobenzene as the solvent results in a different structure of the synthesized product, which is as follows: See Table 1 for details.

[0083] Example 9

[0084] The synthesis method of Example 9 is the same as that of Example 1, except that the substrate structure is: The use of N-ethyldiisopropylamine as the base and n-heptane as the solvent resulted in a different product structure, which is as follows: See Table 1 for details.

[0085] Example 10

[0086] The synthesis method of Example 10 is the same as that of Example 1, except that the substrate structure is: The base is 4-dimethylaminopyridine, which results in a different structure of the synthesized product. The product structure is as follows: See Table 1 for details.

[0087] Table 1. Compound number, fifth structure, product structure, and yield.

[0088]

[0089] Compound 7

[0090] 1 H NMR (400MHz, d6-acetone) δ9.2 (s, 1H), 8.38 (d, 1H, J = 10.3Hz), 7.22 (m, 1H), 7.08 (t, 1H, J = 7.8, 7.8Hz) ,7.01(d,1H,J=6.6Hz),6.96–6.84(m,2H),4.12(q,2H,J=7.0,7.0,7.0Hz),1.37(t,3H,J=7.0,7.0Hz);

[0091] 13 C NMR (101MHz, d6-acetone) δ205.74,160.39,148.38,133.20,133.15,127.28,126.94,124.82,120.77,120.34,111.57,64.13,14.05;

[0092] 19 F NMR(376MHz,d6-acetone)δ-65.23(s,3F);

[0093] HRMS(ESI)m / z:[M+Na] + calcd.for C 12 H 12 F3NNaO2 282.0820; found:282.0714.

[0094] Compound 8

[0095] 1 H NMR (400MHz, CDCl3) δ8.35 (d, 1H, J = 7.9, 7.9Hz), 7.67 (s, 1H), 7.21–7.07 (m, 3H), 6.97–6.82 (m, 1H), 6.69 (dd, 1H, J = 15.3, 2.0Hz);

[0096] 13 C NMR (126MHz, CDCl3) δ160.37,153.54,151.59,130.69,130.18,129.90,125.57,125.50,124.82,124.79,123.40,122.02,121.24,114.93;

[0097] 19 F NMR (376MHz, CDCl3) δ-65.10 (s, 3F), δ-130.51 (s, 1F);

[0098] HRMS(ESI)m / z:[M+Na] + calcd.for C 10 H7F4NNaO 256.0464; found:256.0359.

[0099] Compound 9

[0100] 1 H NMR (400MHz, CDCl3) δ7.69 (s, 1H), 7.14 (s, 1H), 6.94 (d, 2H, J = 8.9Hz), 6.87 (d, 1H, J = 6.7Hz), 6.67 (d, 1H, J = 13.8Hz), 2.27 (s, 3H);

[0101] 13 C NMR (101MHz, CDCl3) δ161.77,160.67,132.76,130.60,130.01,129.66,125.67,125.58,117.45,117.22,113.70,113.48,17.96;

[0102] 19 F NMR (376MHz, CDCl3) δ-65.00 (s, 3F), δ-115.59 (s, 1F);

[0103] HRMS(ESI)m / z:[M+Na] + calcd.for C 11 H9F4NNaO 270.0620; found:270.0512.

[0104] Compound 10

[0105] 1 H NMR(400MHz,d6-acetone)δ9.89(m,1H),8.21–8.12(m,1H),8.05(d,1H,J=7.7Hz),7.99–7.90 (m,1H),7.80(d,1H,J=8.3Hz),7.59–7.46(m,3H),7.33(dd,1H,J=15.4,2.2Hz),6.98(m,1H);

[0106] 13 C NMR(126MHz,d6-acetone)δ205.63,161.19,134.21,132.96,132.91,132.70,128.43 ,127.49,127.33,127.21,126.16,126.11,125.95,125.48,124.31,121.81,120.99;

[0107] 19 F NMR(376MHz,d6-acetone)δ-65.08(s,3F);

[0108] HRMS(ESI)m / z:[M+Na] + calcd.for C 14 H 10 F3NNaO 288.2352; found:288.0605.

[0109] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing a β-trifluoromethyl unsaturated amide, characterized in that, Includes the following steps: (1) Aromatic amine, palladium catalyst, phosphorus ligand, base, solvent and 1-chloro-3,3,3-trifluoropropene are placed in a high-pressure reactor for reaction, and carbon monoxide is introduced into the high-pressure reactor and heated for reaction; (2) After the reaction was complete, the carbon monoxide was stopped, dichloromethane was added to dilute the reaction solution, the organic solvent was removed by rotary evaporation, and the remaining product was separated and purified by silica gel column chromatography to obtain β-trifluoromethyl unsaturated amide. The structure of the β-trifluoromethyl unsaturated amide is shown below: Wherein, R is selected from phenyl, substituted phenyl, The substituents of the substituted phenyl group are selected from any one or more of alkoxy groups having 1-8 carbon atoms, alkyl groups having 1-8 carbon atoms, halogen groups, or nitro groups; In step (1), the palladium catalyst is any one of palladium acetate, bis(triphenylphosphine) palladium chloride, bis(cyanobenzene) palladium dichloride, bisacetonitrile palladium chloride, tetra(triphenylphosphine) palladium, bis(dibenzylacetone) palladium or allyl palladium(II) chloride dimer; In step (1), the phosphorus ligand is any one of 2-bicyclohexylphosphine-2',6'-diisopropoxybiphenyl, tritert-tert-butylphosphine tetrafluoroborate, 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene, 2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl, 1,1'-binaphthyl-2,2'-bis(diphenylphosphine), tri(2-furanyl)phosphine, or 2-dicyclohexylphosphine-2'-methylbiphenyl. In step (1), the base is any one of potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, triethylamine, cesium acetate, 1,8-diazabicycloundecane, N-ethyldiisopropylamine, 4-dimethylaminopyridine, or N,N-diethylaniline.

2. The method for synthesizing β-trifluoromethyl unsaturated amide according to claim 1, characterized in that: In step (1), the aromatic amine is aniline, substituted aniline, The substituents of substituted aniline are selected from any one or more of alkoxy groups having 1-8 carbon atoms, alkyl groups having 1-8 carbon atoms, halogen groups, or nitro groups.

3. The method for synthesizing β-trifluoromethyl unsaturated amide according to claim 1, characterized in that: In step (1), the solvent is any one of tetrahydrofuran, toluene, 1,4-dioxane, acetonitrile, 1,2-dichloroethane, N,N-dimethylformamide, trifluorotoluene, chlorobenzene, or n-heptane.

4. The method for synthesizing β-trifluoromethyl unsaturated amide according to claim 1, characterized in that: In step (1), the pressure of carbon monoxide is 10 atm, the reaction time is 12 h, and the reaction temperature is 80-100℃; the mass ratio of aromatic amine, palladium catalyst, phosphorus ligand, base, solvent and 1-chloro-3,3,3-trifluoropropene is 1:0.03:0.05:2:2:

2.

5. The method for synthesizing β-trifluoromethyl unsaturated amide according to claim 1, characterized in that: In step (2), chromatographic separation is performed using a 200-300 mesh silica gel column.

6. The method for synthesizing β-trifluoromethyl unsaturated amide according to claim 1, characterized in that: In step (2), the eluent used for chromatographic separation is a mixture of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of (10-6):1.

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