Diphosgene → Methyl 3-methylanthranilate

Temperature

60 °C

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.

1. temperatureAfter cooling to room temperature
2. filtrationthe mixture was filtered
3. washthe precipitate was rinsed with hexanes
4. customdried in vacuo
5. customto afford 28.49 g of an off white solid
6. stirringthe resulting solution was stirred at 60° C. for 2 days
7. customThe cooled reaction mixture
8. extractionextracted three times with ethyl acetate
9. dry with materialThe combined organic phases were dried (MgSO4)
10. concentrationconcentrated under reduced pressure

ORD record

ord-969c5453dae34b9aa6584a144c9f4236

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05962436