2-bromo-1-(2,4,5-trifluorophenyl)ethanone

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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)+. The suspension was cooled to about −10° C. for about 15 min the solid was collected by vacuum filtration washed with additional ACN (150 mL) dried under vacuum

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 L 3-neck round bottom flask was charged with 1-(2,4,5-trifluorophenyl)ethanone (49.7 g, 285 mmol) and DCM (350 mL). The flask was equipped with a 250 mL dropping funnel that contained a solution of bromine (14.6 mL, 283 mmol) in DCM (125 mL). This solution was added to the reaction flask over about 1 h at about 23° C. Once addition of the solution was complete, the reaction mixture was stirred for about 1 h at about 23° C. Ice water was added to the reaction flask and the layers were stirred for about 15 min. The layers were separated and the organic solution was then washed with water and brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give the title compound as a pale yellow solid (70.3 g, 97%): LC/MS (Table 1, Method b) Rt=2.20 min; MS m/z 251.0/253.0 (M+H)+. The flask was equipped with a 250 mL This solution was added to the reaction flask over about 1 h at about 23° C Once addition of the solution the layers were stirred for about 15 min The layers were separated the organic solution was then washed with water and brine dried over MgSO4 filtered the solvent was removed under reduced pressure

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom flask was charged with 2-bromo-1-(2,4,5-trifluorophenyl)ethanone (50.0 g, 198 mmol), oxazole-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 with stirring to the remaining residue. 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)+. The suspension was cooled to about −10° C. for about 15 min the solid was collected by vacuum filtration washed with additional ACN (150 mL) dried under vacuum

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 L 3-neck round bottom flask was charged with 1-(2,4,5-trifluorophenyl)ethanone (49.7 g, 285 mmol) and DCM (350 mL). The flask was equipped with a 250 mL dropping funnel that contained a solution of bromine (14.6 mL, 283 mmol) in DCM (125 mL). This solution was added to the reaction flask over about 1 h at about 23° C. Once addition of the solution was complete, the reaction mixture was stirred for about 1 h at about 23° C. Ice water was added to the reaction flask and the layers were stirred for about 15 min. The layers were separated and the organic solution was then washed with water and brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give the title compound as a pale yellow solid (70.3 g, 97%): LC/MS (Table 1, Method b) Rt=2.20 min; MS m/z 251.0 (M+H)+. The flask was equipped with a 250 mL This solution was added to the reaction flask over about 1 h at about 23° C Once addition of the solution the layers were stirred for about 15 min The layers were separated the organic solution was then washed with water and brine dried over MgSO4 filtered the solvent was removed under reduced pressure

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom flask was charged with 2-bromo-1-(2,4,5-trifluorophenyl)ethanone (50.0 g, 198 mmol; Example #N.1), oxazole-2-amine (11.1 g, 132 mmol; GL Synthesis), 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 with stirring to the remaining residue. 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 d) Rt=2.11 min; MS m/z 239.1 (M+H)+. The suspension was cooled to about −10° C. for about 15 min the solid was collected by vacuum filtration washed with additional ACN (150 mL) dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 L 3-neck round bottom flask was charged with 2′,4′,5′-trifluorophenylacetophenone (49.7 g, 285 mmol) and DCM (350 mL). The flask was equipped with a 250 mL dropping funnel that contained a solution of bromine (14.6 mL, 283 mmol) in DCM (125 mL). This solution was added to the reaction flask over about 1 h at about 23° C. Once addition of the solution was complete, the reaction mixture was stirred for about 1 h at ambient temperature. Ice water was added to the reaction flask and the mixture was stirred for about 15 min. The layers were separated and the organic solution was then washed with water and brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give the title compound as a pale yellow solid (70.3 g, 97%): LC/MS (Table 1, Method d) Rt=2.20 min; MS m/z 251.0 (M+H)+. The flask was equipped with a 250 mL This solution was added to the reaction flask over about 1 h at about 23° C Once addition of the solution the mixture was stirred for about 15 min The layers were separated the organic solution was then washed with water and brine dried over MgSO4 filtered the solvent was removed under reduced pressure