Preparation method of 2-amino-N-(2,2,2-trifluoroethyl)acetamide or its salt

Abstract

The present invention relates to a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide or a salt thereof, and belongs to the field of pharmaceutical chemistry. The preparation method comprises reacting a raw material with an amine or ammonium, and preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide or a salt thereof through post-treatment. The preparation method provided by the present invention has low impurities in the obtained product, mild reaction conditions, simple post-treatment, low energy consumption, can reduce costs, and is conducive to industrial implementation.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical chemistry, and in particular to a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide or a salt thereof. Background Art

[0002] 2-Amino-N-(2,2,2-trifluoroethyl)acetamide, usually in the form of a stable salt, is a key intermediate in the synthesis of a new broad-spectrum veterinary insecticide, fluralaner. Fluralaner belongs to the class of isoxazoline animal insecticides, which works by interfering with γ-aminobutyric acid (GABA)-gated chloride ion channels. Compared with animal insecticides such as phenylpyrazoles, cyclopentadienes and macrolides, it has significant differences in molecular structure, site of action, selectivity and cross-resistance, and is safe for mammals and has high insecticidal activity.

[0003] In Chinese patent CN107353222, glycine protected by N-phthaloyl reacts with trifluoroethylamine or its salt to form amide, and the protecting group is removed under the action of hydrazine hydrate to obtain crude 2-amino-N-(2,2,2-trifluoroethyl)acetamide, and the crude product is reacted with acid to form a salt to obtain a salt of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, and finally a base is added to free pure 2-amino-N-(2,2,2-trifluoroethyl)acetamide.

[0004] Anhui University Journal (Natural Science Edition, 2017(5):96-101) reported that under low temperature and alkaline conditions, glycine was reacted with di-tert-butyl carbonate to obtain N-(tert-butyloxycarbonyl)glycine (Compound 1), and then Compound 1 was amidated with trifluoroethylamine hydrochloride in the presence of N,N'-dicyclohexylcarbodiimide and 4-dimethylaminopyridine to obtain N-[2-oxo-2[(2,2,2-trifluoroethyl)amino]ethyl]carbamic acid-1,1-dimethylethyl ester (Compound 2), and then Compound 2 was deprotected with Boc protecting group in the presence of hydrochloric acid to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide, and finally hydrogen chloride gas was introduced to prepare 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride; the reaction formula is shown below.

[0005]

[0006] Chinese patent CN103124721 reports two synthetic routes (route 1 and route 2) for 2-amino-N-(2,2,2-trifluoroethyl)acetamide. Route 1 is to use N-benzyloxycarbonylglycine as raw material and condensation agent carbonyldiimidazole (CDI), and the intermediate formed is directly reacted with trifluoroethylamine hydrochloride without separation. A particularly useful method for removing the benzyl protecting group is to remove the protecting group by hydrogenolysis with hydrogen and palladium carbon catalysis; Route 2 is to use chloroacetyl chloride as the starting material, and at a temperature of -5°C to 0°C, chloroacetyl chloride is added dropwise to a mixture of trifluoroethylamine and carbonate (using a mixed solvent of ethyl acetate and water) and stirred for reaction. The obtained chloroacetamide is then reacted with dibenzylamine under tertiary amine base conditions, using methanol as solvent, heated to reflux, and finally hydrogenolysis with hydrogen to remove the benzyl group. The hydrogenolysis reaction needs to be carried out at a pressure of 5MPa and a temperature of 50 to 80°C.

[0007] Route 1:

[0008]

[0009] Route 2:

[0010]

[0011] The methods for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide disclosed in the above prior art have at least one of the following defects:

[0012] (1) The reaction needs to be carried out under high pressure, which is harsh and not conducive to industrial production;

[0013] (2) The reaction requires the use of condensation agents such as CDI or DCC, which are expensive and have high production costs;

[0014] (3) The reaction has many steps, which easily produces a large amount of pollutants and is not conducive to environmental protection.

[0015] (4) Post-processing is complicated, which is not conducive to industrial production.

[0016] Therefore, it is necessary to develop a safe, environmentally friendly, low-cost, and easy-to-operate method for synthesizing a 2-amino-N-(2,2,2-trifluoroethyl)acetamide intermediate. Summary of the invention

[0017] In a first aspect, the present invention provides a method for preparing a compound of formula (C). A method for preparing a compound of formula (C) comprises:

[0018]

[0019] In the presence of dichloromethane, water and an inorganic base, the compound of formula (A) or its salt undergoes a condensation reaction with the compound of formula (B). After the reaction is completed, the temperature of the reaction solution is controlled to be not less than 20° C. The solution is allowed to stand for separation, the organic layers are combined, and the organic phase is distilled under reduced pressure to obtain a compound of formula (C).

[0020] The molar ratio of the compound of formula (A) or its salt to the compound of formula (B) may be 1:1-1:1.5. In some embodiments, the molar ratio of the compound of formula (A) or its salt to the compound of formula (B) is 1:1-1:1.3. In some embodiments, the molar ratio of the compound of formula (A) or its salt to the compound of formula (B) is 1:1.04.

[0021] The molar ratio of the compound of formula (A) or its salt to the inorganic base can be 1:1-1:3. In some embodiments, the molar ratio of the compound of formula (A) or its salt to the inorganic base is 1:2.

[0022] The inorganic base may include at least one selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, potassium hydroxide, potassium tert-butoxide, and potassium carbonate. In some embodiments, the inorganic base is at least one selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, potassium hydroxide, potassium tert-butoxide, and potassium carbonate.

[0023] The reaction temperature of the condensation reaction may be -10°C to 20°C. In some embodiments, the condensation reaction temperature is -5°C to 10°C. In some embodiments, the condensation reaction temperature is 0°C to 5°C.

[0024] In some embodiments, the method for preparing a compound of formula (C) comprises: in the presence of dichloromethane, water and an inorganic base, condensing 2,2,2-trifluoroethylamine or a salt thereof with chloroacetyl chloride at -10°C-20°C, after the reaction is completed, controlling the temperature of the reaction solution to not less than 20°C, standing for separation, combining the organic layers, and distilling the organic phase under reduced pressure to obtain a compound of formula (C); wherein the molar ratio of 2,2,2-trifluoroethylamine or a salt thereof to chloroacetyl chloride is 1:1-1:1.5; the molar ratio of 2,2,2-trifluoroethylamine or a salt thereof to the inorganic base is 1:1-1:3; and the inorganic base is at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, potassium hydroxide, potassium tert-butoxide, and potassium carbonate.

[0025] The above reaction can be monitored by gas chromatography (GC) to determine the end point of the reaction. When the amount of the compound represented by formula (A) is less than 0.1%, the reaction is considered to be complete. The reaction time is usually less than 2 hours.

[0026] In a second aspect, the present invention provides a method for preparing a compound of formula (D) or a salt thereof. A method for preparing a compound of formula (D) comprises:

[0027]

[0028] The compound of formula (C) or its salt is reacted with amine or ammonium in a reaction solvent at 20°C-80°C, and then post-treated to obtain the compound of formula (D) or its salt.

[0029] The compound of formula (C) or its salt can be prepared according to the above method, or other suitable methods.

[0030] The reaction solvent may include at least one selected from water, ammonia, methanol, ethanol, and isopropanol. In some embodiments, the reaction solvent is ammonia.

[0031] The amine or ammonium may include at least one selected from ammonia water, ammonium carbonate, ammonium bicarbonate, hexamethylenetetramine, ammonium dihydrogen phosphate, diammonium hydrogen phosphate, and ammonium acetate. In some embodiments, the amine or ammonium is ammonia water.

[0032] In some embodiments, the reaction temperature of the reaction with amine or ammonium is 30° C. to 50° C. In some embodiments, the reaction temperature is 40° C.

[0033] The molar ratio of the compound of formula (C) or its salt to the amine or ammonium may be 1:7-1:10. In some embodiments, the molar ratio of the compound of formula (C) or its salt to the amine or ammonium is 1:7-1:9. In some embodiments, the molar ratio of the compound of formula (C) or its salt to the amine or ammonium is 1:8.

[0034] The post-treatment comprises: mixing the reaction solution obtained after the reaction is completed with a base and a first organic solvent, adding an inorganic salt to saturate the aqueous phase, separating the liquids, extracting, combining the organic layers, and distilling the organic layers under reduced pressure to obtain a crude product of the compound of formula (D) or its salt; then mixing the crude product of the compound of formula (D) or its salt with a second organic solvent, adjusting the pH to pH ≤ 2 with an acid, filtering, and drying to obtain the compound of formula (D) or its salt.

[0035] In some embodiments, the post-treatment comprises: mixing the reaction solution obtained after the reaction is completed with a second organic solvent, slurrying, filtering, and vacuum drying to obtain a compound of formula (D) or a salt thereof.

[0036] The first organic solvent may include at least one selected from n-butanol, toluene, 1,2-dichloroethane, dichloromethane, ethyl acetate, isopropyl acetate, n-hexane, methyl tert-butyl ether, and isopropyl ether. In some embodiments, the first organic solvent is at least one selected from n-butanol, toluene, 1,2-dichloroethane, dichloromethane, ethyl acetate, isopropyl acetate, n-hexane, methyl tert-butyl ether, and isopropyl ether.

[0037] The second organic solvent may include at least one selected from ethyl acetate, ethyl formate, methyl acetate, isopropyl acetate, butyl acetate, and ethyl butyrate. In some embodiments, the second organic solvent is at least one selected from ethyl acetate, ethyl formate, methyl acetate, isopropyl acetate, butyl acetate, and ethyl butyrate.

[0038] The base may include at least one selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, potassium hydroxide, potassium tert-butoxide, and potassium carbonate. In some embodiments, the base is at least one selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, potassium hydroxide, potassium tert-butoxide, and potassium carbonate. In some embodiments, the base is sodium hydroxide, which is beneficial to operation control and acquisition of target products.

[0039] The base can be in any suitable amount, so that the system after the reaction solution is mixed with the base and the first organic solvent is alkaline, with a pH greater than 7. In some embodiments, the amount of the base is any suitable amount that can make the pH of the system greater than 8. In some embodiments, the amount of the base is any suitable amount that can make the pH of the system greater than 10.

[0040] The inorganic salt may include at least one selected from sodium chloride, potassium chloride, ammonium chloride, sodium sulfate, potassium sulfate, sodium bisulfate, potassium bisulfate, ammonium sulfate, potassium carbonate, potassium bicarbonate, sodium acetate, and ammonium acetate. In some embodiments, the inorganic salt is at least one selected from sodium chloride, potassium chloride, ammonium chloride, sodium sulfate, potassium sulfate, sodium bisulfate, potassium bisulfate, ammonium sulfate, potassium carbonate, potassium bicarbonate, sodium acetate, and ammonium acetate. In some embodiments, the inorganic salt is sodium chloride, which is more conducive to operation and control.

[0041] In the method provided by the present invention, the free base or acid addition salt of each raw material can be used for the reaction; by controlling the appropriate alkaline conditions, each product in the form of a free base can be obtained, and the appropriate acidic conditions can also be controlled to obtain an acid addition salt, such as a compound of formula (C) or a compound of formula (D); or an acid addition salt such as the hydrochloride of the compound of formula (C) or the hydrochloride of the compound of formula (D) can be obtained.

[0042] Compared with the prior art, the technical solution of the present invention has at least the following technical effects:

[0043] (1) The reaction conditions are mild, which is conducive to industrial production;

[0044] (2) The reagents used are safe and environmentally friendly and are unlikely to cause harm to production personnel and the environment;

[0045] (3) Simple post-processing;

[0046] (4) Low production cost, which is conducive to industrial production;

[0047] (5) The product has high purity and high yield.

[0048] Terminology Note:

[0049] In the description of the present invention, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0050] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0051] In the present invention, expressions such as "compound A" and "compound represented by formula A" refer to the same compound.

[0052] The term "room temperature" refers to a temperature between about 20°C and 35°C, or between about 23°C and 28°C, or about 25°C.

[0053] The reaction involved in the present invention can be monitored by gas chromatography (GC) to find the end point of the reaction. When the detection shows that the reaction raw material compound is less than 0.1%, the reaction is considered to be finished. The reaction time is usually less than 2.5 hours.

[0054] In the method of the present invention, gas chromatography (GC) can be used to monitor the purity of the reactants. DETAILED DESCRIPTION

[0055] In order to enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to further describe the present invention in detail.

[0056] The reagents used in the present invention can be purchased from the market or prepared by the method described in the present invention.

[0057] In the present invention, L represents liter, mL represents milliliter, mol / L represents mole per liter, h represents hour, g represents gram, mg represents milligram, °C represents degree Celsius, GC represents gas chromatography, dichloromethane represents dichloromethane, and W / W represents mass ratio.

[0058] In the present invention, the ammonia water used is an analytically pure aqueous solution containing about 25% ammonia.

[0059] Example 1: Preparation of 2-chloro-N-(2,2,2-trifluoroethyl)acetamide

[0060] Add trifluoroethylamine hydrochloride (100.00 g) and water (100.00 g) to the reaction flask, stir and cool in a -5°C low-temperature tank; add pre-cooled 30% sodium hydroxide aqueous solution (200.00 g) and dichloromethane (300.0 g); add chloroacetyl chloride dichloromethane solution (86.62 g chloroacetyl chloride dissolved in 100 g dichloromethane) dropwise at an internal temperature of 0-5°C, and continue to react at 0-5°C for 1.5 h (sampling and GC measurement, trifluoroethylamine <0.1% indicates complete reaction); transfer to room temperature, stir and heat to the bottle temperature above 20°C, and stand to separate the liquids; take the organic phase and evaporate to dryness under reduced pressure at 40°C to obtain 2-chloro-N-(2,2,2-trifluoroethyl)acetamide: 128.23 g of white solid, yield 99.00%, GC detection, purity 99.33%.

[0061] Example 2: Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride

[0062] Add 2-chloro-N-(2,2,2-trifluoroethyl)acetamide (120.00 g) and aqueous ammonia (960.00 g) into the reaction flask, react at 40°C for 2 h, take 2 drops of samples for GC analysis (2-chloro-N-(2,2,2-trifluoroethyl)acetamide <0.1%, indicating that the reaction is complete); evaporate to dryness under reduced pressure at 60-70°C to obtain 132.79 g of a white solid (take 3 mg of the sample, add 1 mL of 1 mol / L sodium carbonate aqueous solution to dissolve, extract with 1.5 mL of dichloromethane, take the lower layer of solution for GC analysis, purity 93.26%).

[0063] Ethyl acetate (240.00 g) was added to the white solid obtained by evaporation, and the mixture was slurried at room temperature for 2 h; the mixture was filtered, and the filter cake was rinsed with 50 g of ethyl acetate and dried in a vacuum oven at 50°C for 8 h to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride: 118.05 g of white solid with a yield of 89.68%. The purity was 99.17% after sampling and GC analysis.

[0064] 1H NMR (400MHz, DMSO-d6) δ9.34(t,J=5.9Hz,1H),8.17(s,2H),4.07–3.88(m,2H),3.64(s,2H).

[0065] Example 3: Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride

[0066] Add 2-chloro-N-(2,2,2-trifluoroethyl)acetamide (120.00 g) and ammonia water (960.00 g) into the reaction flask, react at 40° C. for 2 h, take 2 drops of samples for GC measurement (2-chloro-N-(2,2,2-trifluoroethyl)acetamide <0.1% indicates that the reaction is complete); evaporate to dryness under reduced pressure at 60-70° C. to obtain 135.13 g of a white solid (take 3 mg of the sample, add 1 mL of 1 mol / L sodium carbonate aqueous solution to dissolve, extract with 1.5 mL of dichloromethane, take the lower layer of solution for GC measurement, purity 92.28%);

[0067] Add 240.00 g of 20% aqueous sodium hydroxide solution (W / W) to the white solid obtained by evaporation. After dissolving, add 840.00 g of n-butanol and solid sodium chloride until the aqueous phase is saturated. Stir at room temperature for 0.5 h and separate the liquids. Add 420.00 g of n-butanol to the aqueous phase, extract, and combine the organic phases. Evaporate the organic phase at 60°C to dryness under reduced pressure to obtain a solid (sample 3 mg, add 1 mL 1 mol / L sodium carbonate aqueous solution was dissolved, 1.5 mL of dichloromethane was extracted, and the lower layer solution was measured by GC, with a purity of 93.36%); 840.00 g of ethyl acetate was added to the obtained solid to dissolve it, and a solution of hydrogen chloride in ethyl acetate was added dropwise until the pH was ≤ 2, and a white solid was precipitated by stirring. The filter cake was filtered, and 60.00 g of ethyl acetate was added to rinse it, and it was dried under vacuum at 50°C for 12 h to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride: 126.86 g of white solid, with a yield of 96.37%, and a sample was taken for GC measurement, with a purity of 99.28%.

[0068] Example 4: Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride

[0069] Add 2-chloro-N-(2,2,2-trifluoroethyl)acetamide (120.00 g) and ammonia water (960.00 g) into the reaction flask, react at 40° C. for 2 h, take 2 drops of samples for GC measurement (2-chloro-N-(2,2,2-trifluoroethyl)acetamide <0.1% indicates that the reaction is complete); evaporate to dryness under reduced pressure at 60-70° C. to obtain 136.56 g of a white solid (take 3 mg of the sample, add 1 mL of 1 mol / L sodium carbonate aqueous solution to dissolve, extract with 1.5 mL of dichloromethane, take the lower layer of solution for GC measurement, purity 93.07%);

[0070] Add 240.00 g of 20% aqueous sodium hydroxide solution (W / W) to the white solid obtained by evaporation, add 840.00 g of dichloromethane after dissolving, add sodium chloride solid until the aqueous phase is saturated, stir at room temperature for 0.5 h, separate the liquids; add 420.00 g of dichloromethane to the aqueous phase, extract, and combine the organic phases; the organic phase is evaporated to dryness under reduced pressure at 60°C to obtain a solid (sample 3 mg, add 1 mL of 1 mol / L aqueous sodium carbonate solution to dissolve, extract with 1.5 mL of dichloromethane, take the lower layer solution and measure GC, purity 9 4.31%); 840.00g of isopropyl acetate was added to the obtained solid to dissolve, and a solution of isopropyl acetate in hydrogen chloride was added dropwise until the pH was ≤2, and a white solid was precipitated by stirring. The filter cake was filtered, and 60.00g of isopropyl acetate was added to rinse the filter cake, and it was dried under vacuum at 50°C for 12h to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride: 121.96g of white solid, with a yield of 92.65%, and a sample was taken for GC measurement, with a purity of 99.12%.

[0071] Example 5: Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride

[0072] Add 2-chloro-N-(2,2,2-trifluoroethyl)acetamide (120.00 g), ammonium carbonate (656.87 g) and 960.00 g of water to the reaction flask, react at 40° C. for 2 h, take 2 drops of samples for GC measurement (2-chloro-N-(2,2,2-trifluoroethyl)acetamide < 0.1% indicates that the reaction is complete); evaporate to dryness under reduced pressure at 60-70° C. to obtain 137.45 g of a white solid (take 3 mg of the sample, add 1 mL of 1 mol / L sodium carbonate aqueous solution to dissolve, extract with 1.5 mL of dichloromethane, take the lower layer of solution for GC measurement, purity 92.85%);

[0073] Add 240.00 g of 20% aqueous sodium hydroxide solution (W / W) to the white solid obtained by evaporation. After dissolving, add 840.00 g of ethyl acetate. Add sodium chloride solid until the aqueous phase is saturated. Stir at room temperature for 0.5 h, separate the liquids, add 420.00 g of ethyl acetate to the aqueous phase, extract, combine the organic phases, and evaporate the organic phases at 60°C under reduced pressure to obtain a solid (sample 3 mg, add 1 mL The mixture was dissolved in 1 mol / L sodium carbonate aqueous solution, extracted with 1.5 mL of dichloromethane, and the lower layer solution was measured by GC, with a purity of 93.16%). 840.00 g of ethyl acetate was added to the obtained solid to dissolve it. A solution of hydrogen chloride in ethyl acetate was added dropwise to the above organic phase until the pH was ≤ 2. A white solid was precipitated by stirring, and the filter cake was filtered off with suction. 60.00 g of ethyl acetate was added to rinse the filter cake, and it was dried under vacuum at 50°C for 12 h to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride: 123.11 g of white solid, with a yield of 93.50%. The sample was taken for GC measurement, and the purity was 99.36%.

[0074] The method of the present invention has been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein within the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims

1. A method for preparing a salt of a compound of formula (D), comprising: The compound of formula (C) or its salt is reacted with 25% aqueous ammonia solution at 20°C-80°C, and then post-treated to obtain a salt of the compound of formula (D); or the compound of formula (C) or its salt is reacted with ammonium carbonate in water at 20°C-80°C, and then post-treated to obtain the salt of the compound of formula (D); The post-treatment comprises: mixing the reaction solution obtained after the reaction is completed with a base and a first organic solvent, adding an inorganic salt to saturate the aqueous phase, separating the liquids, extracting, combining the organic layers, and distilling the organic layers under reduced pressure to obtain a crude product of the compound of formula (D); then mixing the crude product of the compound of formula (D) with a second organic solvent, adjusting the pH to pH≤2 with an acid, filtering, and drying to obtain a salt of the compound of formula (D); or the post-treatment comprises: mixing the reaction solution obtained after the reaction is completed with a second organic solvent, slurrying, filtering, and vacuum drying to obtain a salt of the compound of formula (D).

2. The method according to claim 1, wherein the molar ratio of the compound of formula (C) or its salt to 25% aqueous ammonia solution or ammonium carbonate is 1:7-1:

10.

3. The method according to claim 1, wherein the first organic solvent is selected from at least one of n-butanol, toluene, 1,2-dichloroethane, dichloromethane, ethyl acetate, isopropyl acetate, n-hexane, methyl tert-butyl ether, and isopropyl ether; and the second organic solvent is selected from at least one of ethyl acetate, ethyl formate, methyl acetate, isopropyl acetate, butyl acetate, and ethyl butyrate.

4. The method according to claim 1, wherein the alkali is selected from at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, potassium hydroxide, potassium tert-butoxide and potassium carbonate.

5. The method according to claim 1, wherein in the post-treatment, after the reaction solution is mixed with the base and the first organic solvent, the pH of the system is greater than 7.

6. The method according to claim 1, wherein the inorganic salt is selected from at least one of sodium chloride, potassium chloride, ammonium chloride, sodium sulfate, potassium sulfate, sodium bisulfate, potassium bisulfate, ammonium sulfate, potassium carbonate and potassium bicarbonate.

7. The method according to any one of claims 1 to 6, further comprising: In the presence of dichloromethane, water and an inorganic base, 2,2,2-trifluoroethylamine or its salt and chloroacetyl chloride are subjected to a condensation reaction at -10°C to 20°C. After the reaction is completed, the temperature of the reaction liquid is controlled to be not less than 20°C, the liquid is allowed to stand for separation, the organic layers are combined, and the organic phase is subjected to reduced pressure distillation to obtain a compound of formula (C); wherein: the molar ratio of 2,2,2-trifluoroethylamine or its salt to chloroacetyl chloride is 1:1-1:1.5; the molar ratio of 2,2,2-trifluoroethylamine or its salt to the inorganic base is 1:1-1:3; and the inorganic base is at least one of sodium hydroxide, potassium hydroxide and potassium carbonate.

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