[F:1][C:2]1[N:14]=[CH:13][CH:12]=[C:11]([F:15])[C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[Li+].CC([N-]C(C)C)C.CCCCCCC.[Br:31]C(Br)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Br:31][C:12]1[CH:13]=[N:14][C:2]([F:1])=[C:3]([C:11]=1[F:15])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]
Into a solution of tert-butyl 2,4-difluoronicotinate (0.95 g, 4.4 mmol) in THF (15 mL) at −78° C. was added a solution of LDA in heptane (1.5 M×3.5 mL, 5.3 mmol) dropwise. The mixture was stirred for 10 min. Then a solution of dibromotetrachloroethane (1.86 g, 5.7 mmol) in THF (4.0 mL) was added dropwise. After 15 min, the temperature was allowed to rise to room temperature slowly. The reaction was quenched with saturated NH4Cl. The mixture was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated to give a residue, which was purified by silica chromatography (5-50% dichloromethane in hexanes) to give tert-butyl 5-bromo-2,4-difluoronicotinate (0.55 g, 42%).
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