Acetanilide → 4-(4-Acetamidophenyl)-4-oxobutanoic acid

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Reaction Steps

To a flask charged with anhydrous aluminum chloride (128.1 g, 0.961 mol) was added dropwise neat dimethylformamide (21 mL, 0.27 mol) at a rate such that the internal temperature remained below 70° C. The resulting mixture was thoroughly mixed. To the stirred thick mixture was added in ten portions a mixture of acetanilide (13.53 g, 0.100 mol) and succinic anhydride (10.01 g, 0.100 mol) that had been preground together with a mortar and pestle. The addition rate was controlled to keep the internal temperature at less than or equal to 72° C. The resulting mixture was stirred at 65° C. to 70° C. for 1.25 hours, then poured hot onto ice (1.0 kg). The mixture was acidified with concentrated hydrochloric acid (60 mL), and the resulting solids were filtered. The filtercake was washed with 0.05 M hydrocloric acid and allowed to air dry overnight. The filtercake was suspended in hot water (93 mL), methanol (120 mL) was added, and the hot cloudy solution was gravity filtered. The filtrate was boiled down to 100 mL volume and allowed to cool. The solids were filtered, washed with water-methanol, and dried in vacuo to give 10.03 g of 4-(4-acetylamino-phenyl)-4-oxo-butyric acid as a tan solid.

Provenance & Evidence