Acetic Anhydride → 2-Chloro-4-fluorobenzoic acid

2.1 g (20 mmol) of acetic anhydride were added dropwise at 0° C. to a mixture of 2.0 g (8 mmol) of 2-chloro-4-fluoro-4'-methylbenzophenone, 9.9 g (0.07 mol) of disodium hydrogenphosphate and 3.8 g (40 mmol) of urea/hydrogen peroxide adduct in 50 ml of dichloromethane. The resulting mixture was then allowed to warmup to room temperature. After 12 h at 20° C., it was neutralized with sodium hydrogencarbonate solution and the aqueous phase was subsequently extracted with dichloromethane. The solvent was then distilled off from the organic phase under vacuum. 50 g of 70% sulfuric acid were added to the residue (2.5 g, containing ca. 80% of phenyl 2-chloro-4-fluorobenzoate) and the mixture was heated for 6 h at the boiling point. Dilution of the cooled mixture, extraction with methyl tert-butyl ether, drying, removal of the solvent and recrystallization of the crude product from water gives 1.0 g (5.7 mmol, 72%) of 2-chloro-4-fluorobenzoic acid in the form of a colorless powder (m.p. 182°-186° C.).

1. customto warmup to room temperature
2. extractionthe aqueous phase was subsequently extracted with dichloromethane
3. distillationThe solvent was then distilled off from the organic phase under vacuum
4. addition50 g of 70% sulfuric acid were added to the residue (2.5 g, containing ca. 80% of phenyl 2-chloro-4-fluorobenzoate)
5. temperaturethe mixture was heated for 6 h at the boiling point
6. extractionDilution of the cooled mixture, extraction with methyl tert-butyl ether
7. customdrying
8. customremoval of the solvent and recrystallization of the crude product from water

ORD record

ord-84fcd39159054df084b1121972d5a272

Source dataset

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05481032