Diphosgene → Methyl 3-methylanthranilate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-amino-3-methylbenzoic acid (25.0 g, 165 mmol) in p-dioxane (43 mL) under a nitrogen atmosphere was added diphosgene (20 mL, 165 mmol) and the resulting solution was stirred at 60° C. overnight. After cooling to room temperature, the mixture was filtered and the precipitate was rinsed with hexanes and dried in vacuo to afford 28.49 g of an off white solid. Without further characterization, this material was suspended in dry dimethylformamide (320 mL) and methanol (11.7 mL). 4-Dimethylaminopyridine (3.9 g) was added to this suspension and the resulting solution was stirred at 60° C. for 2 days. The cooled reaction mixture was diluted with saturated sodium bicarbonate solution and saturated ammonium chloride solution and extracted three times with ethyl acetate. The combined organic phases were dried (MgSO4) and concentrated under reduced pressure to yield the title compound of Step A (25.40 g) as an oil. 1H NMR (CDCl3): δ 7.73 (d, 1H), 7.10 (d, 1H), 6.52 (dd,1H), 5.85 (br s,2H), 3.80 (s,3H), 2.07 (s,3H). This material was used in Step B without further characterization.

Provenance & Evidence