1-Bromo-4-fluorobenzene → 2-Fluoro-6-(4-fluorophenyl)pyridine

HRID 1457740Notes

Reaction equation

C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](F)[N:16]=1>C(OCC)C>[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:16]=1

Participants

Conditions

Temperature: -40 °C

Procedure

Butyl lithium (105.0 mL, 0.26 mol, 2.5M solution in hexane) is added to a solution of 1-bromo-4-fluoro benzene (34.3 mL, 0.31 mol) in anhydrous diethyl ether (200 mL) at -20° C. The mixture is stirred for 60 min and then chilled to -40° C. 2,6-Difluoropyridine (22.7 mL, 0.25 mol) is added and the reaction mixture is allowed to warm to ambient temperature. Subsequently, the mixture is washed with saturated aqueous ammonium chloride (300 mL). The layers are separated and the aqueous layer is washed with diethyl ether 3 times (100 mL each). After drying of the combined organic layers with anhydrous magnesium sulphate, the solvent is removed in vacuo. The crude product is purified by flash column chromatography (silica gel, hexane/AcOEt 8/2) yielding colorless crystals of 2-fluoro-6-(4'-fluorophenyl)-pyridine (19.8 g, 41.0% of th.) with mp 34° C.

Workup

temperatureto warm to ambient temperature
washSubsequently, the mixture is washed with saturated aqueous ammonium chloride (300 mL)
customThe layers are separated
washthe aqueous layer is washed with diethyl ether 3 times (100 mL each)
dry with materialAfter drying of the combined organic layers with anhydrous magnesium sulphate
customthe solvent is removed in vacuo
customThe crude product is purified by flash column chromatography (silica gel, hexane/AcOEt 8/2)

Sources & evidence

ORD record: ord-68ceeba76a6447ef8a6ff0b283959347
Source dataset: uspto-grants-1998_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05849758

Reaction notes

Loading…