Chloroacetyl chloride → N-[3-(2-Chloroacetamido)propyl]-2-methylprop-2-enamide

Participants

Reaction Conditions

Reaction Steps

In a 3-liter 4-neck flask fitted with condenser, stirrer, and 2-dropping funnels were placed N-(3-aminopropyl)methacrylamide hydrochloride (157 g 0.88 moles) in methanol (1.2 L) and 2,6-di-tert-butyl-p-cresol (1.0 g). In one funnel was placed chloroacetyl chloride (100 g, 0.89 mole), and in funnel two was placed triethylamine (178 g, 1.76 mole). The solution was cooled to 0°-5° C. (ice-methanol), and triethylamine was added in a slow stream over 30 minutes, and the chloroacetyl chloride was added over 1 hour. After the addition, the temperature was maintained at 0° C. for 2 hours, the ice bath was removed, and stirring was continued at room temperature overnight. The solvent was removed, and to the residue was added hot ethyl acetate (500 mL). The mixture was filtered to remove triethylamine hydrochloride, then the solid was washed with hot ethyl acetate (500 mL), filtered again, the filtrate combined, and the solvent was removed on a rotary evaporator. The residue was crystallized from ethyl acetate (400 mL) by heating to dissolve, filtering to remove any solid present, and cooling to 0° C. to crystallize. The crude monomer was purified by chromatography on a silica gel packed column. The product was eluted from the column using a 1:1 mixture of ethyl acetate and dichloromethane (4 L). The collected solvent was evaporated, and the residue crystallized from ethyl acetate (300 mL) with 2,6-ditert-butyl-p-cresol (500 mg) to give a white crystalline compound, mp 85°-90° C., 83 g (43% yield). Analysis Calculated C9H15ClN2O2 : C, 49.4; H, 6.9; N, 12.8; Cl, 16.2. Found: C, 49.0; H, 7.6; N, 13.2; Cl, 17.3.

Provenance & Evidence