Glycol monoethyl ether → 4-Fluoro-2-(2-fluoro-phenylamino)-benzoic acid

Participants

Reaction Conditions

Reaction Steps

In a 50 mL round bottom flask, 2-bromo-4-fluorobenzoic acid (12.78 g, 58.4 mmol), 2-fluoroaniline (7.33 mL, 75.9 mmol), potassium carbonate (9.68 g, 70.0 mmol), copper (0.371 g, 5.84 mmol) and copper (I) iodide (0.556 g, 2.92 mmol) were added to 2-ethoxyethanol (50 mL). The mixture was heated to 135° C. overnight. The mixture was cooled and 100 mL of water was added. The slurry was stirred at room temperature overnight. The slurry was filtered through a bed of celite and washed with 2-ethoxyethanol. The pH of the filtrate was adjusted to 2 using 4N HCl and the solid was filtered off. The solid was then dried in high vacuum to give 4-fluoro-2-(2-fluoro-phenylamino)-benzoic acid (16.5 g, >100% yield).

Provenance & Evidence