4-Fluorophenol → 3-Bromo-5-(4-fluorophenoxy)pyridine

Sodium hydride (1.53 g of 80% in mineral oil, 51 mmol) was slowly added to a solution of 4-fluorophenol (5.6 g, 50 mmol) in DMF (100 mL) as it was stirred and cooled (ice water bath) under a nitrogen atmosphere. The resulting mixture was warmed to ambient temperature and stirred for 1 h. 3,5-Dibromopyridine (5.9 g, 25 mmol) was added and the mixture was then heated at 90° C. (bath temperature) for 62 h. The mixture was cooled, diluted with water (150 mL), poured into 5N sodium hydroxide (150 mL), and extracted with diethyl ether (2×150 mL). The combined ether extracts were washed with water, dried (MgSO4), filtered and concentrated by rotary evaporation. The residue was purified by flash chromatography on silica gel, using 5% ethyl acetate:hexane as eluent, to yield 1.4 g (21%) of a colorless oil.

1. stirringstirred for 1 h
2. temperaturethe mixture was then heated at 90° C. (bath temperature) for 62 h
3. temperatureThe mixture was cooled
4. extractionextracted with diethyl ether (2×150 mL)
5. washThe combined ether extracts were washed with water
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation
9. customThe residue was purified by flash chromatography on silica gel

ORD record

ord-8aade8a04c6e4434b04d077cde5d80c5

Source dataset

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06852721B2