1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone

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

Procedure: Hydrazine hydrate (3.5 mL, 45 mmol) was added to a solution of 1-(4-bromo-2-fluorophenyI)-2,2,2-trifluoroethanone (1.00 g, 3.69 mmol) in 1-butanol (15 mL). The reaction was heated to reflux for 5 hours, then cooled to room temperature and left stirring overnight. The reaction was diluted with water (50 mL) and extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (310 mg, 32%) as an off-white solid. 1H NMR (400 MHz, CDCl3, δ): 7.42 (dd, J=8.58, 1.56 Hz, 1H), 7.72 (d, J=8.58 Hz, 1H), 7.75 (dd, J=1.56, 0.78 Hz, 1H). The reaction was heated to reflux for 5 hours left extracted with ethyl acetate (3×) The combined organics were washed with brine dried over magnesium sulfate filtered concentrated Purification by flash column chromatography (0-50% ethyl acetate/heptanes)

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

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

Procedure: Hydrazine hydrate (3.5 mL, 45 mmol) was added to a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone (1.00 g, 3.69 mmol) in 1-butanol (15 mL). The reaction was heated to reflux for 5 hours, then cooled to room temperature and left stirring overnight. The reaction was diluted with water (50 mL) and extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (310 mg, 32%) as an off-white solid. 1H NMR (400 MHz, CDCl3, δ): 7.42 (dd, J=8.58, 1.56 Hz, 1H), 7.72 (d, J=8.58 Hz, 1H), 7.75 (dd, J=1.56, 0.78 Hz, 1H). The reaction was heated to reflux for 5 hours left extracted with ethyl acetate (3×) The combined organics were washed with brine dried over magnesium sulfate filtered concentrated Purification by flash column chromatography (0-50% ethyl acetate/heptanes)

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

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

Procedure: Hydrazine hydrate (3.5 mL, 45 mmol) was added to a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone (1.00 g, 3.69 mmol) in 1-butanol (15 mL). The reaction was heated to reflux for 5 hours, then cooled to room temperature and left stirring overnight. The reaction was diluted with water (50 mL) and extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (310 mg, 32%) as an off-white solid. 1H NMR (400 MHz, CDCl3, δ): 7.42 (dd, J=8.58, 1.56 Hz, 1H), 7.72 (d, J=8.58 Hz, 1H), 7.75 (dd, J=1.56, 0.78 Hz, 1H). The reaction was heated to reflux for 5 hours left extracted with ethyl acetate (3×) The combined organics were washed with brine dried over magnesium sulfate filtered concentrated Purification by flash column chromatography (0-50% ethyl acetate/heptanes)

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

Procedure: Hydrazine hydrate (3.5 mL, 45 mmol) was added to a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone (1.00 g, 3.69 mmol) in 1-butanol (15 mL). The reaction was heated to reflux for 5 hours, then cooled to room temperature and left stirring overnight. The reaction was diluted with water (50 mL) and extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (310 mg, 32%) as an off-white solid. 1H NMR (400 MHz, CDCl3, δ): 7.42 (dd, J=8.58, 1.56 Hz, 1H), 7.72 (d, J=8.58 Hz, 1H), 7.75 (dd, J=1.56, 0.78 Hz, 1H). The reaction was heated to reflux for 5 hours left extracted with ethyl acetate (3×) The combined organics were washed with brine dried over magnesium sulfate filtered concentrated Purification by flash column chromatography (0-50% ethyl acetate/heptanes)

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

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

Procedure: To a solution consisting of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanone (3.12 g, 11.5 mmol) and MeOH (50 mL) were added hydroxylamine hydrochloride (4.00 g, 57.5 mmol) and sodium acetate (5.90 g, 71.9 mmol). The resulting mixture was heated at 64° C. for 19 h, at which time additional hydroxylamine hydrochloride (2.40 g, 34.5 mmol) and sodium acetate (3.54 g, 43.1 mmol) were added. Heating was continued for 24 h and the mixture was cool to rt and the mixture was filtered to remove solids. The filtrate was diluted with EtOAc (150 mL), washed with water (150 mL), dried (Na2SO4) and concentrated. The title compound was obtained as a 70:30 ratio of the E and Z oxime isomers (3.28 g, 100%). were added Heating the mixture was filtered to remove solids The filtrate was diluted with EtOAc (150 mL) washed with water (150 mL) dried (Na2SO4) concentrated

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

Procedure: Dess-Martin periodinane (16.57 g, 39.06 mmol) was added to a solution consisting of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanol (10.66 g, 39.06 mmol) and DCM (100 mL) and the resultant mixture was stirred at rt for 1.5 h. Na2S2O3 (10% aq., 100 mL) was added and the resulting mixture extracted with CH2Cl2 (100 mL). The organic layer was washed with Na2S2O3 (50 mL×2), NaHCO3 (satd. aq., 100 mL×2), and brine (100 mL×2). The organic layer was dried (Na2SO4) and concentrated. The crude material was purified (FCC) to yield the title compound (3.20 g, 30%). the resulting mixture extracted with CH2Cl2 (100 mL) The organic layer was washed with Na2S2O3 (50 mL×2), NaHCO3 (satd. aq., 100 mL×2), and brine (100 mL×2) The organic layer was dried (Na2SO4) concentrated The crude material was purified (FCC)

Conditions: temp:64.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution consisting of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanone (3.12 g, 11.5 mmol) and MeOH (50 mL) was added hydroxylamine hydrochloride (4.00 g, 57.5 mmol) and sodium acetate (5.90 g, 71.9 mmol). The resulting mixture was heated at 64° C. for 19 h, after which time additional hydroxylamine hydrochloride (2.40 g, 34.5 mmol) and sodium acetate (3.54 g, 43.1 mmol) were added. Heating was continued for 24 h and the mixture filtered to remove solids. The filtrate was diluted with EtOAc (150 mL), washed with water (150 mL), dried (Na2SO4) and concentrated. The title compound was obtained as a 70:30 ratio of the E and Z oxime isomers (3.28 g, 100%). Heating the mixture filtered to remove solids The filtrate was diluted with EtOAc (150 mL) washed with water (150 mL) dried (Na2SO4) concentrated

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

Procedure: Dess-Martin periodinane (16.57 g, 39.06 mmol) was added to a solution of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanol (10.66 g, 39.06 mmol) in DCM (100 mL) and the reaction mixture was stirred at rt for 1.5 h. Na2S2O3 (10% aq., 100 mL) was added and the resulting mixture extracted with CH2Cl2 (100 mL). The organic layer was washed with Na2S2O3 (50 mL×2), NaHCO3 (satd. aq., 100 mL×2), and brine (100 mL×2). The organic layers were dried (Na2SO4) and concentrated. The crude material was purified (FCC) to yield the title compound (3.20 g, 30%). the resulting mixture extracted with CH2Cl2 (100 mL) The organic layer was washed with Na2S2O3 (50 mL×2), NaHCO3 (satd. aq., 100 mL×2), and brine (100 mL×2) The organic layers were dried (Na2SO4) concentrated The crude material was purified (FCC)