Trifluoroacetic anhydride → 4-(Methylamino)-3-(trifluoromethyl)benzoic acid

Temperature

45 °C

4-amino-3-trifluoromethylbenzoic acid (3.6 g) was suspended in trifluoroacetic anhydride (90 ml) and the suspension was stirred overnight. The solvent was distilled off under vacuum and the resulting residue was dissolved in acetone (30 ml). Methyl iodide (9.9 g) was added to the solution and the mixture was heated to 45° C.; with vigorous stirring, a potassium hydroxide powder (6.8 g) was added slowly, followed by further stirring for 1 h at 45° C. Then, the solvent was distilled off under vacuum and the resulting residue was dissolved in water (50 ml). The solution was heated under reflux for 2 h. The reaction solution was then adjusted to pH of 3.5 with 1N HCl under cooling with ice. The white precipitate was recovered by filtration and washed with a small amount of water and vacuum-dried to yield the end product (2.2 g).

1. distillationThe solvent was distilled off under vacuum
2. dissolutionthe resulting residue was dissolved in acetone (30 ml)
3. additionMethyl iodide (9.9 g) was added to the solution
4. additionwith vigorous stirring, a potassium hydroxide powder (6.8 g) was added slowly
5. stirringby further stirring for 1 h at 45° C
6. distillationThen, the solvent was distilled off under vacuum
7. dissolutionthe resulting residue was dissolved in water (50 ml)
8. temperatureThe solution was heated
9. temperatureunder reflux for 2 h
10. temperatureunder cooling with ice
11. filtrationThe white precipitate was recovered by filtration
12. washwashed with a small amount of water
13. customvacuum-dried

ORD record

ord-bc6a352bd37445f09f02bff79b18aa35

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06559149B1