Tetrabutylammonium Fluoride → 5-Bromo-3-fluoropyridine-2-carbonitrile

At room temperature, to a tetrahydrofuran solution (60 ml) of 5-bromo-3-nitropyridine-2-carbonitrile (6.00 g) was added a tetrahydrofuran solution (1 M, 52.8 ml) of tetrabutylammonium fluoride, followed by stirring for 1 hour. The reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 5-bromo-3-fluoropyridine-2-carbonitrile. To a mixed solvent solution of this in 1,2-dimethoxyethane (120 ml) and water (30 ml) were added 2-hydroxyphenylboronic acid (4.37 g), sodium carbonate (8.39 g) and tetrakis(triphenylphosphine)palladium (1.52 g), followed by stirring under heating at reflux for 2 hours. The reaction solution was brought back to room temperature, poured into ice water, and extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 3-fluoro-5-(2-hydroxyphenyl)pyridine-2-carbonitrile (2.73 g).

1. extractionextracted with ethyl acetate
2. washThe organic layer was washed sequentially with water and saturated sodium chloride solution
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified by silica gel column chromatography

ORD record

ord-9b137b9f9bd543d0911e68a3582dd0d6

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729095B2