[F:1][C:2]([F:15])([F:14])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][N:6]=1.Cl.[CH3:17][NH:18][O:19][CH3:20].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CC(N(C)C)=O>[CH3:20][O:19][N:18]([CH3:17])[C:9](=[O:11])[C:8]1[CH:12]=[CH:13][C:5]([O:4][CH2:3][C:2]([F:1])([F:15])[F:14])=[N:6][CH:7]=1A mixture of 6-(2,2,2-trifluoroethoxy)nicotinic acid (10.4 g, 47.3 mmol, Step-1), N,O-dimethylhydroxylamine hydrochloride (5.08 g, 52.1 mmol), HOBT (9.59 g, 71.0 mmol), EDC (13.6 g, 71.0 mmol) and triethylamine (26.4 mL, 189 mmol) in DMA (237 mL) is stirred at 60° C. for 16 hours. The reaction mixture is poured into saturated aqueous sodium hydrogen carbonate (300 mL) and extracted with EtOAc (500 mL). The organic layer is washed with saturated aqueous sodium hydrogen carbonate (300 mL×2) and dried over sodium sulfate. After filtration, the filtrate is concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (4:1) to give 6.54 g (52% yield) of the title compound as colorless oil.
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