[H-].[Na+].[CH3:3][O:4][CH2:5][CH2:6][OH:7].F[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[N:10]=1>CN(C=O)C>[F:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([O:7][CH2:6][CH2:5][O:4][CH3:3])[N:10]=1Sodium hydride (60 wt % dispersion in mineral oil, 2.51 g, 62.8 mmol) (Aldrich) was added to a stirred mixture of anhydrous 2-methoxyethanol (Aldrich, 2.87 mL, 36.4 mmol) and DMF (30 mL) at 0° C. After 30 min of stirring at 0° C. the reaction mixture turned into a white solid. It was then treated with 2,6-difluoropyridine (3.00 mL, 33.1 mmol) (Aldrich) and allowed to warm to room temperature over 1.5 h. The reaction was quenched with a saturated aqueous solution of NaHCO3 and stirred for 1 h, partitioned between EtOAc and the layers were separated. The organic layer was washed with saturated aqueous NaHCO3, brine, dried (MgSO4), filtered, and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (40 g column, 0-5% EtOAc in hexanes) to give 2-fluoro-6-(2-methoxyethoxy)pyridine (3.0769 g, 17.98 mmol, 54% yield) as a viscous, clear colorless oil. m/z (ESI, +ve ion) 172.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 7.64 (1H, q, J=8.2 Hz); 6.67 (1H, dd, J=8.0, 1.0 Hz); 6.46 (1H, dd, J=7.8, 2.3 Hz); 4.41-4.47 (2H, m); 3.70-3.76 (2H, m); 3.44 (3H, s).
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