Phenylacetylene → HCID 57330204, compound

Participants

Reaction Steps

To a stirred solution of optically enriched (4R,5R)-4-(5-bromopyridin-3-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one (1.25 g, 3.25 mmol) in triethylamine (70 mL) was added ethynylbenzene (0.592 mL, 5.28 mmol), copper(I) iodide (67 mg, 0.352 mmol), and triphenylphosphine (653 mg, 2.464 mmol). Nitrogen was bubbled through the mixture for 10 minutes before adding dichlorobis(triphenylphosphine)-palladium(II) (202 mg, 0.282 mmol) with continued nitrogen gas bubbling. After an additional 10 minutes the reaction mixture was heated to reflux for 16 hours, cooled to ambient temperature, diluted with EtOAc, washed with water (3×), brine, dried over magnesium sulfate, and concentrated in vacuo. Column chromatography (25%-->40% EtOAc/Hex) provided optically enriched (4R,5R)-5-(2,5-difluorophenyl)-4-(5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one which was separated by chiral SFC chromatography (Chiralcel OJ-H preparative column, 30×250 mm, 5 μm, Mobile Phase: 40% MeOH (0.1% DEA) in CO2 @ 150 Bar, Temp: 35° C., Flow rate: 70.0 mL/min. for 16 min, UV monitored @ 280 nM. tR=9.23 min) to provide (1.38 g, 2.99 mmol, 85% yield) of pure single enantiomer (4R,5R)-5-(2,5-difluorophenyl)-4-(5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.77 (d, J=2.21 Hz, 1H) 8.57 (s, 1H) 8.56 (d, J=2.20 Hz, 1H) 8.07 (t, J=2.05 Hz, 1H) 7.58-7.66 (m, 2H) 7.44-7.52 (m, 3H) 7.39-7.45 (m, 1H) 7.28-7.39 (m, 2H) 5.67 (d, J=6.62 Hz, 1H) 5.04 (d, J=6.62 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ ppm 157.28; 157.24 (d, J=240.70 Hz) 155.92 (d, J=245.20 Hz) 151.63; 147.70; 136.78; 135.02; 131.57; 129.43; 128.89; 126.63 (dd, J=14.99, 7.72 Hz) 121.51; 119.47; 117.83 (dd, J=23.60, 9.10 Hz) 117.50 (dd, J=24.50, 8.20 Hz); 114.60 (dd, J=26.34, 4.54 Hz); 92.86; 85.76; 78.12; 59.43; LCMS (ESI) m/z calcd for C22H15F2N2O2: 377.11. found 377.20 [M+H]+; HRMS (ESI) m/z calcd for C22H15F2N2O2: 377.1096. found 377.1096 [M+H]+.

Provenance & Evidence