Acetic Acid → 2-Amino-5-Chloro-N,3-Dimethylbenzamide

Participants

Reaction Conditions

Reaction Steps

A 300-mL flask equipped with a thermometer and nitrogen bubbler was charged with ethyl acetate (100 mL) and 12.6 g (0.21 mol) of acetic acid. Anhydrous methylamine (6.3 g, 0.20 mol) was added below the surface of the liquid mixture, which was cooled to maintain the temperature below 35° C. Then 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (21 g, 0.10 mol) (i.e. the product of Example 1) was added in portions while maintaining the reaction mixture at 35-40° C. After completion of the addition of the 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione the temperature was maintained at 40-45° C., and the progress of the reaction was monitored by HPLC analysis. After about 20 minutes, when no more than 0.5% 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione remained, water (50 mL) was added. A distillation head was attached, moderate vacuum was applied, and ethyl acetate was distilled out at an internal temperature of about 46-60° C. and pressure of about 30 to 50 kPa. To replace the ethyl acetate removed by distillation, water was added to maintain the original liquid volume in the reactor. When a significant amount of water began to distill, the aqueous slurry was cooled to 10° C. The solid was collected by filtration and dried at 60° C. and 13.3 kPa to afford the title compound as a white crystalline solid (19 g, ca. 95% yield, >98% purity by peak area in HPLC analysis).

Provenance & Evidence