4-Bromo-4'-fluoro-1,1'-biphenyl → 3-[2-(4'-Fluorobiphenyl-4-yl)ethynyl]quinuclidin-3-ol

Participants

Reaction Steps

A mixture of 4-bromo-4'-fluorobiphenyl (1.0 g), 3-ethynyl-3-hydroxyquinuclidine (600 mg), bis(triphenylphosphine)-palladium (II) chloride (120 mg) and copper (I) iodide (60 mg) in dry triethylamine (15 ml) was stirred at reflux under an atmosphere of argon for 5 hours. The reaction mixture was cooled, diluted with water (60 ml), 2H aqueous sodium hydroxide solution added and extracted with dichloromethane. The mixed layers were filtered through diatomaceous earth and washed with dichloromethane. The organic layer in the filtrate was separated, dried (MgSO4) and evaporated to a residue which was further purified by flash column chromatography on alumina (ICN Alumina N 32-63) using a mixture of 10% ethanol in ethyl acetate as eluent to give a residue which was crystallised from a mixture of 10% ethanol in ethyl acetate to give 3-[2-(4'-fluorobiphenyl-4-yl)ethynyl]quinuclidin-3-ol (210 mg) as a solid, m.p. 232-233° C.; microanalysis, found: C, 78.0; H, 6.4; N, 4.5%; C21H20FN0.O.1H2O requires C,78.07; H,6.26; N, 4.34%; NMR (DMSO-d6): 1.2-1.4(1H, m), 1.5-1.7(1H, m), 1.8-2.01(3H, m), 2.6-2.8(4H, t), 2.8-3.15(2H, d of d), 5.6(1H, s), 7.22-7.4(2H, m), 7.45-7.55(2H, d) and 7.61-7.81(4H, m); m/z 322 (M+H).

Provenance & Evidence