[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14](N(C)C)=[O:15])[CH2:10]1.[C:19]1(C)C=CC=CC=1.C[Mg]Br.Cl>O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14](=[O:15])[CH3:19])[CH2:10]1
A 1000-mL flask equipped with thermometer and addition funnel was charged with 5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide (i.e. the product of Step A) (80.0 g, 0.31 mol) and toluene (320 mL). The reaction mixture was cooled to −5° C., and a solution of methyl magnesium bromide (3.0 M in tetrahydrofuran, 120 mL, 0.36 mmol) was added dropwise while maintaining the reaction temperature between −10 to −5° C. When gas chromatography analysis of the reaction mixture showed about 2% of 5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide remaining, the reaction mixture was poured into a stirred solution of concentrated hydrochloric acid (80 mL) and water (320 mL) while maintaining the temperature of the mixture between 10 to 30° C. The organic layer was separated, washed with saturated aqueous sodium chloride solution (80 mL) and concentrated under reduced pressure. The resulting oil was crystallized from hexanes (100 mL) and collected by filtration washing with hexanes. The resulting solid was dried in a vacuum oven overnight at 23° C. to provide the title compound as a waxy, off-white solid (65 g), melting at 47-50° C.
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