[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:17])[CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[CH:4][CH:3]=1.C([O:22][N:23]=O)(C)(C)C.Cl>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:17])[C:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[N:23][OH:22])=[CH:6][CH:7]=1To a solution of 1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)ethanone (43 g, 0.184 mol) in ethanol (800 mL) at −10° C. was added dropwise t-butylnitrite (24.1 mL, 0.20 mol) over 10 minutes followed by 2.5 M HCl in absolute ethanol (60 mL, 0.15 mol). The reaction temperature was maintained at −5° C. during these additions. After addition was complete, the dry ice bath was removed and the reaction was allowed to warm to RT and stirred overnight. The ethanol was removed under reduced pressure and the residue was diluted with H2O and made basic with saturated NaHCO3. It was extracted with EtOAc, the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude residue was taken up in methanol/isopropanol and mixed with toluene. The methanol/isopropanol mixture was concentrated under reduced pressure and the title compound was recrystallized from hexane/toluene (47.5 g).
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