Cl.[NH2:2][OH:3].[OH-].[K+].[F:6][C:7]1[CH:8]=[C:9]([C:15](=O)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14].O>C(O)C.C1(C)C=CC=CC=1>[F:6][C:7]1[CH:8]=[C:9]([C:15](=[N:2][OH:3])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14]
Hydroxylamine hydrochloride (3.7 g, 53.2 mmol) and potassium hydroxide (2.98 g, 53.2 mmol) were suspended in absolute ethanol (25 mL) and vigorously stirred in a 250-mL round-bottom flask equipped with a magnetic stirring bar under a dry nitrogen blanket for 30 minutes. To this, a suspension of 1-(3-fluoro-4-methoxyphenyl)-2-phenyl-ethan-1-one from Step 1 (10.0 g, 40.9 mmol) in toluene (150 mL) was added in one portion. A Dean-Stark trap and reflux condenser were added to the apparatus, and the yellow suspension was warmed to reflux. The solution was maintained at reflux 16 hours, then the suspension was cooled to room temperature. Water (100 mL) was added, and the resulting solution was extracted with ethyl acetate (2×100 mL). The combined organic solution was washed with brine (100 mL), dried over magnesium sulfate and filtered. The resulting solution was evaporated under reduced pressure to yield a crude residue. The residue was crystallized from boiling ethanol/water to yield, upon filtration and drying, 10.0 g (94%) of 1-(3-fluoro-4-methoxyphenyl)-2 phenyl-ethan-1-one oxime as ivory-colored crystals: 1H NMR (CDCl3 /300 MHz) δ 7.42 (dd, J=12.69, 2.01, 1H), 7.36-7.19 (m, 6H), 6.89 (dd, J=8.66, 8.46 HZ, 1H), 4.16 (s, 2H), 3.88 (s, 3H). 19F NMR (CDCl3 /282.2 MHz): 135.517 (m).
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