C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1.[Li+].CC([N-]C(C)C)C.[CH:29](=[O:36])[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.C(O)(=O)C>C1COCC1.CO.CCOC(C)=O>[F:13][C:14]1[C:19]([CH:29]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)[OH:36])=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1To diisopropylamine (9.3 mL, 66.1 mmol) in THF (100 mL) at −78° C. was added n-BuLi (23.1 mL of a 2.5 M solution in hexanes, 57.8 mmol) dropwise via syringe. 2,6-difluoropyridine (5.0 mL, 55.1 mmol) in THF (100 mL) at −78° C. was added to the above prepared LDA solution dropwise via canula to give a clear yellow-green solution. isonicotinaldehyde (6.3 mL, 66.1 mmol) was added causing a white precipitate to form. The reaction mixture was warmed to room temperature and then glacial acetic acid (3.3 mL, 57.8 mmol) was added. Silica gel was added and the volatiles removed on a rotary evaporator. Flash chromatography (80-100% EtOAc/hexanes-3-5-7% MeOH/EtOAc) gave 8.48 g (69%) of as an off white solid. Rf=0.38 (5% MeOH/EtOAc); MS m/z 223 (M+H)+; 1H NMR (300 MHz, DMSO-D6) δ ppm 5.91 (d, J=4.41 Hz, 1 H) 6.49 (d, J=4.41 Hz, 1 H) 7.20 (dd, J=8.31, 2.54 Hz, 1 H) 7.36 (m, 2 H) 8.19 (m, 1 H) 8.53 (m, 2 H); Found: 223, 221; Anal calcd for C11H8F2N2O: C, 59.46; H, 3.63; N, 12.61. Found: C, 59.45; H, 3.66; N, 12.62.
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