[F:1][C:2]1[C:3](C#N)=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.C[Mg]Br.C(=O)(O)[O-].[Na+].Cl.[NH2:20][OH:21].[C:22]([O-])(=O)[CH3:23].[Na+]>C1COCC1.CCO.O>[F:1][C:2]1[C:3](/[C:22](=[N:20]\[OH:21])/[CH3:23])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1To a solution of 3,5-difluoropicolinonitrile (10.0 g, 71.4 mmol) in THF (200 ml) was added methylmagnesium bromide (61.2 ml, 85.7 mmol) in THF solution at 0° C. The reaction was stirred at room temperature for 1.5 hours. Saturated sodium bicarbonate solution (50 ml) was added, extracted with ether (100 ml), and dried over sodium sulfate. The solvent was removed. The residue (11.2 g, 71.28 mmol), hydroxylamine hydrochloride (9.907 g, 142.6 mmol) and sodium acetate (11.70 g, 142.6 mmol) in EtOH (100 ml) and water (50 ml) was heated at reflux for 3 hours. The solvent was removed and diluted with 50 ml of saturated sodium bicarbonate and extracted with EtOAc (2×200 ml). After dried over sodium sulfate, the solvent was removed and the title compound was used directly in next step without purification.
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