Phenylacetylene → HCID 69093897, compound

Participants

Reaction Steps

To a slurry of (4R,5R)-4-(5-bromopyridin-3-yl)-5-(2-fluorophenyl)oxazolidin-2-one (100 mg, 0.297 mmol; prepared in analogous fashion to the preparation of (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one starting from 2-fluorobenzaldehyde in place of 2,5-difluorobenzaldehyde) in triethylamine (Volume: 5 mL) was bubbled nitrogen for 20 min. Ethynylbenzene (0.049 mL, 0.445 mmol) was added and nitrogen bubbling was continued for 5 min before adding bis(triphenylphosphine) palladium (II) chloride (15.61 mg, 0.022 mmol), triphenylphosphine (14.00 mg, 0.053 mmol), and copper (I) iodide (4.24 mg, 0.022 mmol) in 1 portion. After 5 min of additional nitrogen bubbling, the vessel was placed in a 70° C. bath under nitrogen for 18 h at which time it was cooled and concentrated. The residue was dissolved in methanol and purified via preparative liquid chromatography (Sunfire C18 OBD 30×100 mm 5 μm, A=95% H2O/5% Acetonitrile, B=95% Acetonitrile/5% H2O, Modifier 10 mM Ammonium Acetate, 0.00 min=20% B, 8.0 min=100% B, 13.0 min=100% B, Flow rate=40 mL/min) and then by chiral HPLC (Chiralpak AD 21×250 10 μm, A=Heptane with 0.1% diethylamine, B=Ethanol, Isocratic 50% A, Flow Rate=15 mL/min providing (4R,5R)-5-(2-fluorophenyl)-4-(5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one (61 mg; 57%). 1H NMR (500 MHz, CDCl3) δ ppm 8.78 (1H, d, J=1.83 Hz), 8.48 (1H, d, J=1.83 Hz), 7.92 (1H, t, J=1.98 Hz), 7.56 (2H, dd, J=6.71, 2.75 Hz), 7.46-7.53 (1H, m), 7.34-7.46 (4H, m), 7.20-7.31 (1H, m), 7.06-7.20 (1H, m), 5.58 (1H, d, J=5.80 Hz), 5.44 (1H, br. s.), 4.86 (1H, d, J=5.80 Hz). Mass Spectral Anal. Calcd. for [M+H]+ C22H15FN2O2: 359.1. found 359.1.

Provenance & Evidence