[Br:1][C:2]1[C:3](=[O:17])[NH:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1.[C:18]([O-])([O-])=O.[K+].[K+].[CH:24]1(CBr)[CH2:26][CH2:25]1>CN(C=O)C>[Br:1][C:2]1[C:3](=[O:17])[N:4]([CH:24]2[CH2:26][CH2:25]2)[CH:5]=[C:6]([CH3:18])[C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1To a solution of 3-bromo-4-(4-fluorobenzyloxy)-1H-pyridin-2-one (0.25 g, 0.84 mmol) in DMF (13 mL) was added K2CO3 (0.33 g, 1.7 mmol) and cyclopropylmethyl bromide (0.14 g, 1.0 mmol), and the reaction mixture was stirred at 110° C. for 2 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was diluted with a 50% aqueous solution of brine, and extracted with CHCl3 (3×50 mL). The combined organics were washed with water and then brine, dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:1 EtOAc/hexanes) afforded 3-bromo-1-cyclopropyl-methyl-4-(4-fluorobenzyloxy)-1H-pyridin-2-one as a yellow solid (0.12 g, 39%): mp 139-141° C.; 1H NMR (300 MHz, CDCl3) δ 7.43-7.34 (m, 3H), 7.07 (t, J=9 Hz, 2H), 6.06 (d, J=6 Hz, 1H), 5.19 (s, 2H), 3.82 (d, J=9 Hz, 2H), 1.26-1.23 (m, 1H), 0.62-0.57 (m, 2H), 0.40-0.36 (m, 2H). ES HRMS m/z 352.0368 (M+H C16H16BrFNO2 requires 352.0343).
Loading…
