反应详情

A round bottom flask was charged with 2-bromo-1-(2,4,-difluorophenyl)ethanone (74.8 g, 318 mmol), oxazol-2-amine (GL Synthesis, 22.3 g, 265 mmol), THF (400 mL), and ACN (660 mL). The resulting mixture was stirred at ambient temperature for about 20 h. The resulting suspension was filtered and the solids were washed with Et2O (150 mL) and dried under reduced pressure to give 1-(2,4-difluorophenyl)-2-(2-iminooxazol-3(2H)-yl)ethanone hydrobromide (51.4 g, 61%). A portion of this material (19.8 g, 62.0 mmol) was added in 3 g portions over about 2 h to a flask charged with polyphosphoric acid (124.4 g) at about 80° C. The thick solution was mixed at about 80-90° C. for about 22 h. The reaction mixture was slowly transferred to a mixture of water (150 mL) and 30% aqueous NaOH (150 mL) at about 5-10° C. The pH of the resulting slurry was adjusted to about 5.4 by addition of 30% aqueous NaOH and the product was isolated by filtration. The wet cake was rinsed with warm water (3×150 mL) and dried under vacuum to give the title compound (9.5 g, 69%). MS m/z 221.1 (M+H)+ FIA(APCI)

1. filtrationThe resulting suspension was filtered
2. washthe solids were washed with Et2O (150 mL)
3. customdried under reduced pressure