Phenylacetylene → HCID 69081723, compound

Participants

Reaction Conditions

Reaction Steps

To trans-4-(3-bromophenyl)-5-(pyridin-3-yl)oxazolidin-2-one (46 mg, 0.144 mmol) slurried in triethylamine (3 mL) was added ethynylbenzene (0.021 mL, 0.187 mmol), copper(I) iodide (2.74 mg, 0.014 mmol), and triphenylphosphine (26.5 mg, 0.101 mmol). The reaction mixture was cooled to −78° C. under nitrogen and subjected to three rounds of pump/nitrogen purge. The mixture was then warmed to ambient temperature and (Ph3P)2PdCl2 (10.12 mg, 0.014 mmol) was added. The vessel was fitted with a reflux condensor and placed in an oil bath at 93° C. for 18 h at which time the vessel was removed from the heat and the residue was solubilized in 1:1 dimethylformamide/methanol and purified via preparative HPLC method 4. Pooling and concentration of the fractions containing the peak eluting at 7.37 min provided 14.3 mg trans-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one as an indeterminate enantiomeric mixture. 1H NMR (500 MHz, MeOD) δ ppm 8.44 (1H, d, J=7.32 Hz), 8.16 (1H, br. s.), 7.57-7.63 (2H, m), 7.47-7.57 (4H, m), 7.44 (1H, d, J=7.63 Hz), 7.36-7.42 (4H, m), 5.68 (1H, d, J=6.41 Hz), 4.98 (1H, d, J=6.71 Hz). LC/MS (Analytical HPLC Method 6) 1.97 min, Anal. Calcd. for [M+H]+ C22H16N2O2: 341.12. found 341.29. HPLC retention time (Analytical HPLC method 3): 7.30 min. Further purification via preparative SFC method 5 provided 2.2 mg (4%) (4R,5R)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one (5.8 min retention time) as a colorless oil and 2.0 mg (4%) (4S,5S)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one as a colorless oil. HPLC retention time for (4R,5R)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one (Analytical HPLC method 3): 7.12 min. HPLC retention time for (4S,5S)-4-(3-(phenylethynyl)phenyl)-5-(pyridin-3-yl)oxazolidin-2-one (Analytical HPLC method 3): 7.10 min.

Provenance & Evidence