Water → 4-Bromo-3-fluorobenzoic acid

4-Bromo-3-fluorotoluene (40.0 g, 0.212 mol) was heated at 90° C. in H2O (200 mL)-pyridine (200 mL) with mechanical stirring under Ar. Potassium permanganate (KMnO4) (67 g, 0.424 mol) was added portionwise over 3 h. After 4 h, an HPLC of a filtered sample indicated 50% conversion to the acid. An additional 30 g of KMnO4 was added and heating continued overnight. HPLC indicated 81% conversion. Further KMnO4 was added portionwise with reaction monitoring by HPLC until >95% conversion was obtained. The reaction mixture was filtered through Celite, the filter pad washed with H2O, aq NaOH and EtOH. The filtrate was concentrated to a small volume, then partitioned between 3N NaOH solution and diethyl ether. The aqueous basic layer was separated, cooled in an ice-H2O bath and acidified slowly with 6N HCl solution to precipitate the white solid product. This was collected by suction filtration and dried at 40° C. in a vacuum oven overnight to give the title compound. mp 190-192° C.

1. temperatureheating continued overnight
2. customwas obtained
3. filtrationThe reaction mixture was filtered through Celite
4. washthe filter pad washed with H2O, aq NaOH and EtOH
5. concentrationThe filtrate was concentrated to a small volume
6. custompartitioned between 3N NaOH solution and diethyl ether
7. customThe aqueous basic layer was separated
8. temperaturecooled in an ice-H2O bath
9. customto precipitate the white solid product
10. filtrationThis was collected by suction filtration
11. customdried at 40° C. in a vacuum oven overnight

ORD record

ord-0b72dbd65808469b8568c7061f2f9614

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06566385B2