[H-].[Na+].Cl[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][N:5]=1.[CH3:14][C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1)=O.[OH-:24].[Na+].Cl.[NH2:27]O>CO.COCCOC>[Cl:23][C:19]1[CH:18]=[C:17]([C:15](=[N:27][OH:24])[CH2:14][C:4]2[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][N:5]=2)[CH:22]=[CH:21][CH:20]=1A reaction vessel was charged with sodium hydride (as a 60% oil dispersion, 14.4 g, 360 mmol), DME (120 ml) and 2-chloro-5-trifluoromethylpyridine (20 g, 110 mmol) under nitrogen. 3-Chloroacetophenone (15.5 ml, 200 mmol) was added in portions to the mixture which was stirring at −10° C. The mixture was allowed to warm to ambient temperature and then heated to 40-45° C. for 5 hours. Upon completion of the reaction, the mixture was cooled to 5° C. and 10% aqueous sodium hydroxide solution (60 ml) was slowly added to the reaction mixture followed by methanol (120 ml) then hydroxylamine hydrochloride (38.2 g, 550 mmol). The mixture was heated to 72° C. for 4 hours then cooled and partitioned between water and ethyl acetate, washed with brine and evaporated under vacuum to dryness. The resulting solid was slurried with cyclohexane (60 ml) and dichloromethane (10 ml) then filtered, washing with further cyclohexane. 17.5 g (53%) of the title compound was collected.
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