Hydrochloric Acid → 1-Bromo-4-chloro-3-(difluoromethoxy)-2-fluorobenzene

Temperature

100 °C

To a solution of 3-bromo-6-chloro-2-fluorophenol (1.00 g, 4.44 mmol) and sodium chlorodifluoroacetate in dimethylformamide (DMF; 9 mL) was added potassium carbonate (1.22 g, 5.32 mmol) and water (1.77 mL) and the resulting mixture heated to 100° C. for 4 hours. The solution was cooled to ambient temperature and concentrated hydrochloric acid (2.5 mL) and water (4 mL) were added and stirred at ambient temperature overnight. The solution was cooled in an ice bath and neutralized with 2N sodium hydroxide and then extracted with ethyl ether (2×25 mL). The combined extracts were washed with brine, dried (sodium sulfate), and concentrated to give 1-bromo-4-chloro-2-fluoro-3-difluoromethoxybenzene (1.20 g, 4.2 mmol). This material was used without further purification.

1. temperatureThe solution was cooled to ambient temperature
2. temperatureThe solution was cooled in an ice bath
3. extractionextracted with ethyl ether (2×25 mL)
4. washThe combined extracts were washed with brine
5. dry with materialdried (sodium sulfate)
6. concentrationconcentrated

ORD record

ord-1aaeb1a5cbf84234ad79bcf0802c033b

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07498468B2