Chloroacetyl chloride → 2-chloro-N-(2,4-dimethoxyphenyl)acetamide

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Reaction Conditions

Reaction Steps

A solution was prepared from 15.3 g of 2,4-dimethoxyaniline and 10.1 g of triethylamine in 300 ml of methylenedichloride. The solution was cooled to about 0° C. Eleven and three tenths grams of chloroacetylchloride were added in dropwise fashion with stirring under a nitrogen blanket. After the addition had been completed, the reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was then extracted successively with equal volumes of 1N hydrochloric acid and of water. The organic solution was next extracted with cold saturated aqueous sodium bicarbonate followed by a second extraction with water. All these aqueous extracts were discarded. The organic solution was dried, and the solvent removed in vacuo. A residue consisting of 23 g of a purple colored solid was obtained. Twenty-one grams of this residue were chromatographed over silica gel using ethyl acetate as the eluant in order to remove a colored impurity. Fractions containing the desired product, N-chloroacetyl-2,4-dimethoxyaniline were combined and the solvent removed therefrom to yield a tan solid residue. Recrystallization of the residue from an ethyl acetate/hexane solvent mixture gave 16.5 g of N-chloroacetyl-2,4-dimethoxyaniline melting at 90°-91° C. (yield=72%).

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