Br[C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=3[F:20])[O:11][C:10](=[O:21])[NH:9]2)[CH:5]=[N:6][CH:7]=1.[C:22]([Si](C)(C)C)#[CH:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(N(CC)CC)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[F:20][C:14]1[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=1[C@H:12]1[O:11][C:10](=[O:21])[NH:9][C@@H:8]1[C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:22]#[CH:23])[CH:3]=1To a slurry of (4R,5R)-4-(5-bromopyridin-3-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one (1.00 g, 2.82 mmol) in triethylamine (30 mL) was bubbled nitrogen for 20 min at which time ethynyltrimethylsilane (0.557 mL, 3.94 mmol) was added with continued nitrogen bubbling for 5 min before adding bis(triphenylphosphine) palladium (II) chloride (0.148 g, 0.211 mmol), triphenylphosphine (0.133 g, 0.507 mmol), and copper (I) iodide (0.161 g, 0.845 mmol) together in 1 portion. After 5 min additional bubbling of nitrogen, the vessel was capped and placed in a 70° C. bath. After 18 h, the vessel was cooled to ambient temperature, concentrated in vacuo dissolved in ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to a black tar which was dissolved in methanol (30 mL). Potassium carbonate (0.428 g, 3.10 mmol) was added and after 30 min, the reaction was concentrated and dissolved in ethyl acetate, washed with water, brine, dried over MgSO4, filtered and concentrated in vacuo to a black tar which was loaded with dichloormethane onto a 40 g silica gel cartridge. Elution with 5 to 75% EtOAc/Hex over 6 column volumes then 75% EtOAc over 2 column volumes. Fractions containing the main peak were concentrated to (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one (766 mg; 91%) as a yellow oil which crystallized upon standing. 1H NMR (500 MHz, CDCl3) δ ppm 8.75 (1H, d, J=1.83 Hz), 8.52 (1H, d, J=2.14 Hz), 7.87 (1H, t, J=1.98 Hz), 7.17-7.24 (1H, m), 6.98-7.15 (2H, m), 5.52 (2H, d, J=5.49 Hz), 4.80 (1H, d, J=5.80 Hz), 3.30 (1H, s). Mass Spectral Anal. Calcd. for [M+H]+ C16H10F2N2O2: 301.07. found 301.01.
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