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

Abstract

The invention belongs to the technical field of organic matter synthesis, and relates to a preparation method of 2-amino-N-(2, 2, 2-trifluoroethyl) acetamide, and the 2-amino-N-(2, 2, 2-trifluoroethyl) acetamide is synthesized by dissolving N-(2, 2, 2-trifluoroethyl)-2-haloacetamide, nitrite ester, hydrazine, alkali and a catalyst in an alcohol solvent and carrying out one-pot reaction in the presence of hydrogen. The invention provides a new method for preparing the 2-amino-N-(2, 2, 2-trifluoroethyl) acetamide, provides a new scheme with good yield for the preparation of the 2-amino-N-(2, 2, 2-trifluoroethyl) acetamide, and has important practical significance and practical value.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and specifically, relates to a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide. Background Art

[0002] 2-Amino-N-(2,2,2-trifluoroethyl)acetamide, which usually exists stably in the form of a salt, is a key intermediate for synthesizing the novel broad-spectrum insecticidal and veterinary drug fluralaner.

[0003] Regarding the preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, some preparation methods have been disclosed in patents. For example, Japanese Patent JP5652628B2 discloses a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide or its salt in two steps by reacting chloroacetyl chloride with 2,2,2-trifluoroethylamine and then treating with ammonia in the presence of methyl tert-butyl ether in an autoclave; this method can lead to the formation of the dimer impurity N-(2,2,2-trifluoroethyl)-2-{[(2,2,2-trifluoroethylcarbamoyl)-methyl]-amino}acetamide; the dimer is produced by the continued reaction of the target product with unreacted 2-chloro-N-(2,2,2-trifluoroethyl)acetamide, and this method involves further purification, thereby reducing the yield and increasing the total cost. Japanese Patent JP5652628 discloses a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide using readily available reactants such as phthaloyl chloride; phthaloyl chloride is either an expensive reagent or involves expensive reaction steps with multiple purifications; in addition, this method requires a protecting group to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide; therefore, the whole process becomes expensive and cumbersome, making this process unsuitable for commercial scale. Patent CN107353222A discloses a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide or its salt, which involves condensing N-phthaloylglycine with 2,2,2-trifluoroethylamine hydrochloride under alkaline conditions, followed by deprotection and purification. The preparation of 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-N-(2,2,2-trifluoroethyl)-acetamide from expensive N-phthaloylglycine and 2,2,2-trifluoroethylamine hydrochloride has a yield of only 60% in the presence of 4-dimethylaminopyridine, dichloromethane, and triethylamine; the deprotection of 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-N-(2,2,2-trifluoroethyl)-acetamide to prepare 2-amino-N-(2,2,2-trifluoroethyl)acetamide is carried out in the presence of ethanol, and hydrazine hydrate and its salt are further converted to 2-amino-N-(2,2,2-trifluoroethyl)acetamide in the presence of hydrogen chloride gas, but it may also contain dimer impurities.

[0004] Therefore, in combination with the above, it is of great value to provide a preparation method of 2-amino-N-(2,2,2-trifluoroethyl)acetamide with simple method, convenient post-treatment and good yield. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a preparation method of 2-amino-N-(2,2,2-trifluoroethyl)acetamide.

[0006] To solve the above problems, the technical solution adopted by the present invention is: The present invention provides a preparation method of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, wherein the 2-amino-N-(2,2,2-trifluoroethyl)acetamide is obtained by reacting an alkali, hydrazine hydrate, nitrite, and N-(2,2,2-trifluoroethyl)-2-haloacetamide dissolved in an alcohol solvent under the action of hydrogen and a catalyst.

[0007] As a further preferred embodiment of the present invention, the molar ratio of N-(2,2,2-trifluoroethyl)-2-haloacetamide, nitrite, hydrazine hydrate, and alkali is 1:2-5:2-5:2-5.

[0008] As a further preferred embodiment of the present invention, the nitrite has the structure shown in formula I: ; wherein, R is selected from saturated or unsaturated C1-C5 straight-chain or branched-chain hydrocarbon groups.

[0009] As a further preferred embodiment of the present invention, the nitrite is selected from methyl nitrite, ethyl nitrite, n-propyl nitrite, isopropyl nitrite, n-butyl nitrite, or isoamyl nitrite.

[0010] As a further preferred embodiment of the present invention, the alkali includes one or more of potassium carbonate, sodium carbonate, sodium hydroxide, and potassium hydroxide.

[0011] As a further preferred embodiment of the present invention, the N-(2,2,2-trifluoroethyl)-2-haloacetamide is selected from N-(2,2,2-trifluoroethyl)-2-chloroacetamide or N-(2,2,2-trifluoroethyl)-2-bromoacetamide.

[0012] As a further preferred embodiment of the present invention, the reaction temperature is 40-60°C; the reaction time is 4-6 h.

[0013] As a further preferred embodiment of the present invention, the alcohol solvent is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, or isoamyl alcohol.

[0014] As a further preferred embodiment of the present invention, the pressure of the hydrogen is 10 mmHg to 1 Mpa.

[0015] As a further preferred embodiment of the present invention, the catalyst is selected from 5%-10% palladium on carbon or Raney nickel; the dosage of the catalyst is 1%-5% of the mass of N-(2,2,2-trifluoroethyl)-2-haloacetamide.

[0016] The beneficial effects produced by adopting the above technical solution are as follows: The present invention provides a new method for synthesizing 2-amino-N-(2,2,2-trifluoroethyl)acetamide, which is synthesized in one step from hydrazine hydrate, nitrite and N-(2,2,2-trifluoroethyl)-2-haloacetamide under the conditions of hydrogen and a catalyst, without the need for deprotection and purification. The preparation steps are simple and the operability is high; at the same time, the yield is stably above 75%, and the highest can reach 89.68%. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is the nuclear magnetic resonance hydrogen spectrum of 2-amino-N-(2,2,2-trifluoroethyl)acetamide obtained in Example 1 of the present invention; Figure 2 is the electrospray ionization mass spectrum of 2-amino-N-(2,2,2-trifluoroethyl)acetamide obtained in Example 1 of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0018] To make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be clearly and completely described below with reference to specific embodiments.

[0019] Preparation Example 1 Add 165.83 g of potassium carbonate, 500 mL of water and 500 mL of dichloromethane into a 2 L three-necked flask, and start mechanical stirring. Cool the reaction mixture to below 10 °C, add 135.5 g of 2,2,2-trifluoroethylamine hydrochloride, and then slowly add 236.1 g of bromoacetyl chloride and continue stirring for about 10 minutes. Control the temperature at about 25 °C and keep it for about 3 hours; after standing the reaction, separate the two phases, extract the aqueous layer with 200 mL of dichloromethane again, wash the obtained organic layer with 100 mL of saturated sodium bicarbonate solution, and then wash it with 300 mL of water. The organic layer is vacuum concentrated to remove the solvent at 40-45 °C, and the residue is stirred in 300 mL of petroleum ether for 1-2 hours. Filter to collect the obtained solid, and wash the filter cake with 50 mL of petroleum ether. Subsequently, dry it in a vacuum oven at 45-50 °C for 4-5 hours to obtain N-(2,2,2-trifluoroethyl)-2-bromoacetamide.

[0020] Preparation Example 2 165.83 g of potassium carbonate, 500 mL of water and 500 mL of dichloromethane were added to a 2 L three-necked flask, and mechanical stirring was started. The reaction mixture was cooled to below 10 °C, 135.5 g of 2,2,2-trifluoroethylamine hydrochloride was added, and then 169.39 g of chloroacetyl chloride was slowly added and stirring was continued for about 10 minutes. The temperature was controlled at about 25 °C and maintained for about 3 hours; after standing for the reaction, the two phases were separated, the aqueous layer was extracted again with 200 mL of dichloromethane, the obtained organic layer was washed with 100 mL of saturated sodium bicarbonate solution, and then washed with 300 mL of water. The organic layer was concentrated under vacuum at 40-45 °C to remove the solvent, and the residue was stirred in 300 mL of petroleum ether for 1-2 hours. The obtained solid was collected by filtration, and the filter cake was washed with 50 mL of petroleum ether. Subsequently, it was dried in a vacuum oven at 45-50 °C for 4-5 hours to obtain N-(2,2,2-trifluoroethyl)-2-chloroacetamide.

[0021] Example 1 1 L of methanol and 24 g of NaOH were added to a 5 L autoclave, stirred and dissolved, cooled in an ice-water bath, 22.62 g of 85% hydrazine hydrate was added, the temperature of the solution was maintained at about 20 °C, 36.63 g of methyl nitrite was slowly added, and the temperature of the solution was controlled not to exceed 50 °C. After dissolution, it was kept warm for about 4 hours; it was cooled to about 5 °C by freezing, 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C were added, and then nitrogen was charged 3 times to displace the air, and then replaced with hydrogen. The hydrogen pressure was maintained at 20 mmHg, and it was heated to 45 ± 5 °C and stirred for 6 hours; the palladium carbon was removed by suction filtration, most of the solvent was removed by rotary evaporation of the filtrate, and 1 L of distilled water was added; it was extracted 3 times with 300 mL of ethyl acetate each time, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (27.3 g of yellow oily liquid, yield: 87.44%).

[0022] 1 HNMR(DMSO- d6 ): 7.82(s,1H)3.94-3.89(m,2H)3.40(s,1H); MS-ESI: 157[M+1].

[0023] Example 2 In a 5 L autoclave, add 1 L of methanol and 83 g of K2CO3, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, and keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge the air by filling nitrogen three times, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 27.5 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 88.08%.

[0024] Example 3 In a 5 L autoclave, add 1 L of methanol and 24 g of NaOH, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 53.45 g of isopropyl nitrite, control the solution temperature not to exceed 50 °C, and keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge the air by filling nitrogen three times, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 27.7 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 88.72%.

[0025] Example 4 Add 1 L of methanol and 24 g of NaOH to a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 61.87 g of n-butyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge with nitrogen 3 times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate for 3 times, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 26.7 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 85.51%.

[0026] Example 5 Add 1 L of methanol and 24 g of NaOH to a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 35.2 g of N-(2,2,2-trifluoroethyl)-2-chloroacetamide obtained in Preparation Example 2 and 1.76 g of 5% Pd / C, then purge with nitrogen 3 times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate for 3 times, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 26.8 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 85.61%.

[0027] Example 6 Add 1 L of methanol and 24 g of NaOH into a 5 L autoclave, stir to dissolve, cool down with an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 10% Pd / C, then purge with nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium-carbon, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL × 3 of ethyl acetate, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 24.9 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 79.75%.

[0028] Example 7 Add 1 L of methanol and 24 g of NaOH into a 5 L autoclave, stir to dissolve, cool down with an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of Raney nickel, then purge with nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the Raney nickel, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL × 3 of ethyl acetate, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 23.8 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 76.23%.

[0029] Example 8 Add 1 L of methanol and 24 g of NaOH to a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 0.44 g of 5% Pd / C, then purge with nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 27.0 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 86.47%.

[0030] Example 9 Add 1 L of methanol and 16 g of NaOH to a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 15.08 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 24.42 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge with nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 28 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 89.68%.

[0031] Example 10 Add 1 L of methanol and 40 g of NaOH into a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 37.8 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 61.05 g of methyl nitrite, control the solution temperature not exceeding 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge with nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 24.3 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 77.83%.

[0032] Example 11 Add 1 L of methanol and 24 g of NaOH into a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not exceeding 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge with nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 10 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 26.6 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 85.19%.

[0033] Example 12 In a 5 L autoclave, add 1 L of methanol and 24 g of NaOH, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge the air by filling nitrogen three times, and then replace it with hydrogen, keep the hydrogen pressure at 1 Mpa, heat to 45 ± 5 °C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL × 3 of ethyl acetate, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 23.9 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 76.55%.

[0034] Example 13 In a 5 L autoclave, add 1 L of methanol and 24 g of NaOH, stir to dissolve, cool down in an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 36.63 g of methyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then purge the air by filling nitrogen three times, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 40 °C and stir for 8 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL × 3 of ethyl acetate, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 24.7 g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 79.11%.

[0035] Example 14 In a 5L autoclave, add 1L of methanol and 24g of NaOH, stir to dissolve, cool down in an ice-water bath, add 22.62g of 85% hydrazine hydrate, keep the solution temperature at about 20°C, slowly add 36.63g of methyl nitrite, control the solution temperature not to exceed 50°C, keep warm for about 4 hours after complete dissolution; cool down to about 5°C by freezing, add 44.0g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2g of 5% Pd / C, then purge the air by filling nitrogen 3 times, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 60°C and stir for 4 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1L of distilled water; extract with 300 mL of ethyl acetate for 3 times, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 27.3g of 2-amino-N-(2,2,2-trifluoroethyl)acetamide, with a yield of 87.44%.

[0036] Example 15 In a 5L autoclave, add 1L of isopropanol and 16g of NaOH, stir to dissolve, cool down in an ice-water bath, add 15.08g of 85% hydrazine hydrate, keep the solution temperature at about 20°C, slowly add 30g of ethyl nitrite, control the solution temperature not to exceed 50°C, keep warm for about 4 hours after complete dissolution; cool down to about 5°C by freezing, add 44.0g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 1.1g of 10% Pd / C, then purge the air by filling nitrogen 3 times, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5°C and stir for 6 hours; filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1L of distilled water; extract with 300 mL of ethyl acetate for 3 times, dry with anhydrous sodium sulfate, and filter under reduced pressure to remove the solvent to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (25.1g of yellow oily liquid, yield: 80.39%).

[0037] Example 16 Add 1 L of n-propanol and 33.66 g of KOH into a 5 L autoclave, stir to dissolve, start cooling with an ice-water bath, add 22.62 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 53.46 g of propyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.0 g of 10% Pd / C, charge nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 10 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL × 3 of ethyl acetate, dry with anhydrous sodium sulfate, filter under reduced pressure to remove the solvent to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (26.4 g of yellow oily liquid, yield: 84.55%).

[0038] Example 17 Add 1 L of n-butanol and 40 g of NaOH into a 5 L autoclave, stir to dissolve, cool with an ice-water bath, add 37.8 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 117.46 g of isoamyl nitrite, control the solution temperature not to exceed 50 °C, keep warm for about 4 hours after complete dissolution; cool to about 5 °C by freezing, add 35.2 g of N-(2,2,2-trifluoroethyl)-2-chloroacetamide obtained in Preparation Example 2 and 1.5 g of 5% Pd / C, charge nitrogen three times to displace air, and then replace it with hydrogen, keep the hydrogen pressure at 20 mmHg, heat to 45 ± 5 °C and stir for 6 hours; filter off palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water, extract with 300 mL × 3 of ethyl acetate, dry with anhydrous sodium sulfate, filter under reduced pressure to remove the solvent to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (24.2 g of yellow oily liquid, yield: 77.31%).

[0039] Example 18 Add 1 L of isopentanol and 83 g of K2CO3 to a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, and add 22.62 g of 85% hydrazine hydrate. Keep the solution temperature at about 20 °C, slowly add 70.3 g of isopentyl nitrite, control the solution temperature not to exceed 50 °C, and keep the temperature for about 4 hours after complete dissolution. Cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 0.6 g of Raney nickel. Fill with nitrogen three times to displace the air, and then replace it with hydrogen. Keep the hydrogen pressure at 0.5 Mpa, heat to 45 ± 5 °C and stir for 6 hours. Filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water, extract with 300 mL of ethyl acetate three times, dry with anhydrous sodium sulfate, and filter under reduced pressure to remove the solvent to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (26.9 g of yellow oily liquid, yield: 86.15%).

[0040] Example 19 Add 1 L of 95% ethanol and 63.76 g of Na2CO3 to a 5 L autoclave, stir to dissolve, cool down in an ice-water bath, add 22.68 g of 85% hydrazine hydrate, keep the solution temperature at about 20 °C, slowly add 70.47 g of isopentyl nitrite, control the solution temperature not to exceed 50 °C, and keep the temperature for about 4 hours after complete dissolution. Cool down to about 5 °C by freezing, add 35.2 g of N-(2,2,2-trifluoroethyl)-2-chloroacetamide obtained in Preparation Example 2 and 0.7 g of Raney nickel. Fill with nitrogen three times to displace the air, and then replace it with hydrogen. Keep the hydrogen pressure at 1.0 Mpa, heat to 45 ± 5 °C and stir for 6 hours. Filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water, extract with 300 mL of ethyl acetate three times, dry with anhydrous sodium sulfate, and filter under reduced pressure to remove the solvent to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (23.9 g of yellow oily liquid, yield: 76.35%).

[0041] Comparative Example 1 Dissolve 39 g of sodium azide in 1 L of methanol; cool down to about 5 °C by freezing, add 44.0 g of N-(2,2,2-trifluoroethyl)-2-bromoacetamide obtained in Preparation Example 1 and 2.2 g of 5% Pd / C, then fill with nitrogen three times to displace the air, and then replace it with hydrogen. Keep the hydrogen pressure at 10 mmHg, heat to 45 ± 5 °C and stir for 6 hours. Filter off the palladium carbon by suction, rotary evaporate the filtrate to remove most of the solvent, add 1 L of distilled water; extract with 300 mL of ethyl acetate three times, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 2-amino-N-(2,2,2-trifluoroethyl)acetamide (22 g of yellow oily liquid, yield: 70.46%).

[0042] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide, characterized in that: The 2-amino-N-(2,2,2-trifluoroethyl)acetamide is obtained by dissolving a base, hydrazine hydrate, nitrite and N-(2,2,2-trifluoroethyl)-2-haloacetamide in an alcohol solvent and reacting them under the action of hydrogen and a catalyst.

2. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The molar ratio of the N-(2,2,2-trifluoroethyl)-2-haloacetamide, the nitrite, the hydrazine hydrate and the base is 1:2-5:2-5:2-5.

3. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The nitrite structure is shown in Formula I: ； Wherein, R is selected from saturated or unsaturated C1-C5 straight chain or branched hydrocarbon groups.

4. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The nitrite is selected from methyl nitrite, ethyl nitrite, n-propyl nitrite, isopropyl nitrite, n-butyl nitrite or isoamyl nitrite.

5. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The base includes one or more of potassium carbonate, sodium carbonate, sodium hydroxide and potassium hydroxide.

6. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The N-(2,2,2-trifluoroethyl)-2-haloacetamide is selected from N-(2,2,2-trifluoroethyl)-2-chloroacetamide or N-(2,2,2-trifluoroethyl)-2-bromoacetamide.

7. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The reaction temperature is 40-60° C.; the reaction time is 4-6 hours.

8. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The alcohol solvent is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol or isoamyl alcohol.

9. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The pressure of the hydrogen is 10 mmHg~1 MPa.

10. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide according to claim 1, characterized in that: The catalyst is selected from 5%-10% palladium carbon or Raney nickel; the amount of the catalyst is 1%-5% of the mass of N-(2,2,2-trifluoroethyl)-2-haloacetamide.

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