Tetrahydrofuran → 2-(2-iminooxazol-3(2H)-yl)-1-(2,4,5-trifluorophenyl)ethanone hydrobromide

Participants

Reaction Conditions

Reaction Steps

A round bottom flask was charged with 2-bromo-1-(2,4,5-trifluorophenyl)ethanone (50.0 g, 198 mmol), oxazol-2-amine (GL Synthesis, 11.1 g, 132 mmol), THF (200 mL), and ACN (330 mL). The resulting mixture was stirred at about 23° C. for about 20 h. The suspension was cooled to about −10° C. for about 15 min and the solid was collected by vacuum filtration, washed with additional ACN (150 mL), and dried under vacuum to give 2-(2-iminooxazol-3(2H)-yl)-1-(2,4,5-trifluorophenyl)ethanone hydrobromide (35.1 g, 79%) as a white solid. A portion of this material (20.0 g, 59.3 mmol) was suspended in toluene (140 mL) and the suspension was cooled to about 0° C. To the flask was added a 1.0 M solution of TiCl4 in toluene (154 mL) over about 30 min. The mixture was stirred at about 0° C. for about 30 min and was then heated to about 100° C. for about 3 h. The mixture was cooled to ambient temperature, the toluene was decanted off, and ice was added to the remaining residue with stirring. The mixture was adjusted to about pH 8 with the addition of solid Na2CO3, followed by the addition of EtOAc. The mixture was stirred for about 1 h and then passed through a pad of Celite®. The layers were separated and the organic solution was dried over MgSO4, filtered, and concentrated to dryness under reduced pressure to give the title compound as a white solid (11.7 g, 83%): LC/MS (Table 1, Method b) Rt=2.11 min; MS m/z 239.1 (M+H)+.

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