2-Bromopyridine → 2-(2,4-Difluorophenyl)pyridine

Temperature

-78 °C

That is, under argon stream, 8.69 g (55.0 mmol) of 2-bromopyridine was dissolved in 200 ml of dry tetra hydrofuran and cooled to −78° C. To this was dripped 38.7 ml (61.9 mmol) of a 1.6 M hexane solution of n-butyllithium over 30 minutes. After completion of the dripping, further a solution of 7.5 g (55.0 mmol) of zinc chloride in 50 ml of dry tetra hydrofuran was dripped over 30 minutes. After completion of the dripping, the temperature of the mixture was slowly elevated to 0° C. and 9.65 g (55.0 mmol) of 1-bromo-2,4-difluorobenzene and 2.31 g (2.0 mmol) of tetrakis(triphenylphosphine)palladium (0) were added thereto. The mixture was stirred for 6 hours under reflux and then 200 ml of saturated saline was added to the reaction mixture, followed by extraction of the reaction mixture with diethyl ether. After drying the extract, concentration and purification by column chromatography (silica gel; chloroform/hexane (1/1:volume ratio)) afforded 6.00 g (31.4 mmol) of 2-(2,4-difluorophenyl)pyridine as color less transparent oil. Yield: 63%. Identification was performed by elementary analysis of 1H-NMR and elementary analysis of C, H and N.

1. customover 30 minutes
2. customwas slowly elevated to 0° C.
3. temperatureunder reflux
4. addition200 ml of saturated saline was added to the reaction mixture
5. extractionfollowed by extraction of the reaction mixture with diethyl ether
6. customAfter drying
7. concentrationthe extract, concentration and purification by column chromatography (silica gel; chloroform/hexane (1/1:volume ratio))

ORD record

ord-774d39a309e641678ea6032d72ed45c8

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07396598B2