2-chloro-N-(2,2,2-trifluoroethyl)acetamide synthesis

Yield:170655-44-4 100%

Reaction Conditions:

Stage #1: 2,2,2-trifluoro-ethylamine hydrochloridewith tert-butyl methyl ether;sodium hydroxide in water monomer at 20; for 0.5 h;
Stage #2: chloroacetyl chloride at 5 - 10; for 1 h;

Steps:

1 Preparation of 2-chloro-N- (2,2,2-trifluoroethyl) acetamide

To a 500 ml four-necked flask, 30.4 g (759.3 mmol) of sodium hydroxide and 50 g of water were added, dissolved at room temperature, and then cooled to 5 ° C. A solution prepared by dissolving 50 g (370.4 mmol) of 2,2,2-trifluoroethylamine hydrochloride in 60 g of water was added dropwise thereto at 5 ° C. After 85 g of tert-butyl methyl ether was added and stirred for 30 minutes, a solution of 43.9 g (388.9 mmol) of chloroacetyl chloride dissolved in 15 g of tert-butyl methyl ether was added dropwise while keeping at 5 ° C. The reaction solution was heated to 10 ° C. and stirred for 1 hour. After disappearance of 2,2,2-trifluoroethylamine was confirmed by gas chromatography, the temperature was raised to room temperature and liquid separation was carried out. The aqueous layer was extracted with 100 g of tert-butyl methyl ether, the organic layers were combined, the solvent was distilled off under reduced pressure to adjust the liquid volume, and 2-chloro-N- (2,2,2-trifluoroethyl) acetamide Of a tert-butyl methyl ether solution was obtained. As a result of the internal standardization by high performance liquid chromatography, the yield was 65 g, the yield was 100%, and the concentration was 25.1 wt%. The melting point of 2-chloro-N- (2,2,2-trifluoroethyl) acetamide taken out by dropping the obtained solution in heptane and crystallizing it was 53.8 ° C. (DSC).

References:

JP5652628,2015,B2 Location in patent:Paragraph 0057