Br[C:2]1[CH:3]=[CH:4][C:5]([CH:8]([F:10])[F:9])=[N:6][CH:7]=1.Cl.[CH3:12][NH:13]OC.C1(P(C2C=CC=CC=2)C2[C:36]3[O:35]C4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:66](=[O:69])(O)[O-].[Na+]>C1(C)C=CC=C(C)C=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:9][CH:8]([F:10])[C:5]1[N:6]=[CH:7][C:2]([C:66]([N:13]([O:35][CH3:36])[CH3:12])=[O:69])=[CH:3][CH:4]=1Combine 5-bromo-2-(difluoromethyl)pyridine (5.00 g, 24.03 mmol), N,O-dimethylhydroxylamine hydrochloride (3.52 g, 36.09 mmol), palladium(II) acetate (0.162 g, 0.722 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.695 g, 1.201 mmol), and potassium phosphate (tribasic) (15.3 g, 72.07 mmol) in m-xylene (50 mL). Purge the reaction vessel with carbon monoxide gas. Heat the solution to 100° C., and stir under an atmosphere of carbon monoxide for 16 hours. Safely purge the vessel in a well-ventilated area with nitrogen until it is free of carbon monoxide. Add water (200 mL) to quench the reaction. Adjust the pH of the mixture to 7 with a saturated sodium bicarbonate aqueous solution. Extract the mixture with EtOAc. Dry the combined organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify the resulting residue by silica gel chromatography eluting with a 2:1 ratio of petroleum ether to EtOAc to give the title compound (2.5 g, 48% yield) as a clear oil. LCMS (m/z) 216 (M+1).
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