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Method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide

A technology of trifluoroethyl and trifluoroethylamine, which is applied in the field of preparing 2-amino-N-acetamide and its salts, can solve the problems of harsh conditions, intrinsic safety, high cost, and expensive catalyst, and achieves the reaction conditions Gentle, Inexpensive, Simple Effect

Inactive Publication Date: 2017-11-17
荆门医药工业技术研究院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The two synthetic routes reported in this patent all need to use noble metal catalysts when removing the protecting group on the amino group, and the price of the catalyst is expensive. At the same time, it is necessary to use flammable and explosive hydrogen to carry out in a pressurized reactor. It can be seen that , the synthesis route has relatively harsh conditions in large-scale production, and there are problems of intrinsic safety and high cost, which have certain limitations in actual production

Method used

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  • Method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide
  • Method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide
  • Method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide

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Embodiment 1

[0035] 1) 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-N-(2,2,2-trifluoroethyl)-acetamide (Compound 4) preparation of

[0036] Dissolve phthalylglycine (5.00 g, 0.024 mol) and DMAP (0.44 g, 0.0036 mol) in 200ml of dichloromethane, cool down to below 0°C, add DCC (5.59 g, 0.0288 mol), and at 0°C After stirring for 30 minutes, trifluoroethylamine hydrochloride (3.52 g, 0.026 mol) and triethylamine (6.7 ml, 0.048 mol) were added, and the reaction was continued at room temperature for 12 hours. Cool down to below 0°C, remove the white precipitate by filtration, wash the filtrate with 200ml of water, separate the organic phase, dry over anhydrous magnesium sulfate, filter, concentrate and crystallize to obtain 4.25g of compound 4 (yield 60.9%). 1 H NMR (DMSO- d6 ) : 8.94(tr, J =6.0Hz, 1H), 7.94-7.88(m, 4H), 4.29(s, 2H), 3.99-3.90(m, 2H).

[0037] 2) Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide (compound 1)

[0038] Add compound 4 (4 g, 0.014 mol), 100 ml of ethanol and ...

Embodiment 2

[0041] 1) 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-N-(2,2,2-trifluoroethyl)-acetamide (Compound 4) preparation of

[0042]Dissolve phthalylglycine (5.00 g, 0.024 mol) in 100ml N,N-dimethylformamide, add diisopropylethylamine (12.5ml, 0.072mol) and HATU (13.69g, 0.036mol) After stirring and reacting at room temperature for 1 hour, trifluoroethylamine (2.38 g, 0.024 mol) was added, and the reaction was continued at room temperature for 18 hours. The solvent was removed by rotary evaporation, 100ml of ethyl acetate was added and stirred for 30 minutes, washed with 300ml of water, the organic phase was separated, dried over anhydrous magnesium sulfate, filtered, concentrated and crystallized to obtain 5.12g of compound 4 (yield 73.4%).

[0043] 2) Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide

[0044] Add compound 4 (4.58 g, 0.016 mol), 160 ml of ethanol and 40% hydrazine hydrate (4.0 ml, 0.032 mol) into the reaction flask, stir at 40°C for 8 hours, filter to remove th...

Embodiment 3

[0047] 1) 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-N-(2,2,2-trifluoroethyl)-acetamide (Compound 4) preparation of

[0048] Dissolve phthalylglycine (5.00 g, 0.024 mol) in 200ml ethyl acetate, add CDI (3.89 g, 0.024 mol), stir at room temperature for 1 hour, then add triethylamine (5.0 ml, 0.036mol ) and trifluoroethylamine hydrochloride (3.52 g, 0.026 mol), continue to react at room temperature for 12 hours. The reaction was quenched with 50ml of 1N hydrochloric acid, the organic phase was separated, washed with 200ml of water, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by rotary evaporation to obtain 5.13g of compound 4 (yield 73.5%).

[0049] 2) Preparation of 2-amino-N-(2,2,2-trifluoroethyl)acetamide (compound 1)

[0050] Add compound 4 (4.58 g, 0.016 mol), 60 ml of methanol and 80% hydrazine hydrate (1.3 ml, 0.021 mol) into the reaction flask, stir at room temperature for 24 hours, filter to remove the white precipitate, and spin evapora...

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Abstract

The invention relates to a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide and its salt. The method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide and its salt comprises the following steps: reacting N-phthaloyl-protected glycine with trifluoroethylamine or its salts to form amide, removing the above protective group under the action of hydrazine hydrate to obtain crude2-amino-N-(2,2,2-trifluoroethyl)acetamide, carrying out a salt formation reaction on the crude 2-amino-N-(2,2,2-trifluoroethyl)acetamide and an acid to obtain the salt of the 2-amino-N-(2,2,2-trifluoroethyl)acetamide, and adding an alkali to dissociate the 2-amino-N-(2,2,2-trifluoroethyl)acetamide. The method has the advantages of low price of a deprotection reaction reagent used in the invention, simplicity in operation, no use of flammable and explosive hydrogen, realization of the reaction temperature from room temperature to the reflux temperature of a solvent, and mild reaction conditions, and is very suitable for the production of industrial devices.

Description

technical field [0001] The present invention relates to a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide and salts thereof. Background technique [0002] 2-Amino-N-(2,2,2-trifluoroethyl)acetamide, which usually exists stably in the form of salt, is a key intermediate in the synthesis of a new broad-spectrum insecticidal veterinary drug fluralaner. Freilaner belongs to the isoxazoline animal insecticides, which work by interfering with γ-aminobutyric acid (GABA)-gated chloride ion channels, and interact with phenylpyrazoles, cyclopentadienes and macrolides Compared with other animal insecticides, there are significant differences in molecular structure, action site, selectivity and cross-resistance, etc., and have the characteristics of safety to mammals and high insecticidal activity. [0003] Currently, DuPont's patent CN103124721B in China reports two synthetic routes (route 1 and route 2) about 2-amino-N-(2,2,2-trifluoroethyl)acetamide. [0004] Route 1:...

Claims

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Application Information

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IPC IPC(8): C07C231/12C07C237/06
CPCY02P20/55C07C231/12C07D209/48C07C237/06
Inventor 李强古冬云李立威范伟伟
Owner 荆门医药工业技术研究院
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