4-BROMO-2-(TRIFLUOROMETHYL)BENZALDEHYDE

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Treat a mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (6.52 g, 25.8 mmol) and methanol (250 mL) in a 500 mL flask with sodium borohydride (778 mg, 20.6 mmol). Stir the reaction at room temperature for 1 hour then dilute with ethyl acetate (300 mL). Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL), then dry over anhydrous magnesium sulfate. After filtering, concentrate the solution under vacuum to dryness. Add dimethylformamide (250 mL) to the residue and cool in an ice bath before treating with carbon tetrabromide (12.78 g, 38.5 mmol) and triphenylphosphine (10.11 g, 38.5 mmol) for 3 hours. Add ethyl acetate (300 mL) and wash with water (2×200 mL) then saturated sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate and concentrate under vacuum. Purify the crude product via silica gel chromatography eluting with hexanes to afford 6.02 g (74%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H, J=1.9 Hz), 7.68 (dd, 1H, J=1.9 Hz, J=8.3 Hz), 7.47 (d, 1H, J=8.3 Hz), 4.57 (s, 2H). Treat the reaction at room temperature for 1 hour Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL) dry over anhydrous magnesium sulfate After filtering concentrate the solution under vacuum to dryness Add dimethylformamide (250 mL) to the residue and cool in an ice bath Add ethyl acetate (300 mL) and wash with water (2×200 mL) Dry over anhydrous magnesium sulfate concentrate under vacuum Purify the crude product via silica gel chromatography eluting with hexanes

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

Procedure: Combine 4-bromo-1-(dibromomethyl)-2-(trifluoromethyl)benzene (6.66 g, 16.8 mmol), silver nitrate (14.8 g, 87.3 mmol), THF (250 mL), and water (35 mL) in a 500 mL flask equipped with a magnetic stir bar, reflux condenser, and N2 inlet. Reflux the mixture while stirring for 2.5 hours then cool to room temperature. Filter the reaction through Celite®, add ethyl acetate (250 mL) and wash with water (2×200 mL) then saturated aqueous sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate, concentrate to an orange oil, and purify the crude product via silica gel chromatography eluting with hexanes to afford 3.46 g (81%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 10.35-10.33 (m, 1H), 8.0 (d, 1H, J=8.3 Hz), 7.93 (d, 1H, J=1.4 Hz), 7.86 (dd, 1H, J=1.2 Hz, J=8.3 Hz). reflux condenser, and N2 inlet Reflux the mixture Filter the reaction through Celite® wash with water (2×200 mL) Dry over anhydrous magnesium sulfate concentrate to an orange oil purify the crude product via silica gel chromatography eluting with hexanes

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (9 g), 2-cyano-phenylboric acid (9.5 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (2.9 g), tetrabutylammonium bromide (1.15 g), 2M aqueous sodium carbonate solution (30 mL) and toluene (100 mL) was stirred at 100° C. overnight under an argon atmosphere. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (3.2 g, 32%). washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (9 g), 2-cyano-phenylboric acid (9.5 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (2.9 g), tetrabutylammonium bromide (1.15 g), 2M aqueous sodium carbonate solution (30 mL) and toluene (100 mL) was stirred at 100° C. overnight under an argon atmosphere. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (3.2 g, 32%). washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography

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

Procedure: Treat a mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (6.52 g, 25.8 mmol) and methanol (250 mL) in a 500 mL flask with sodium borohydride (778 mg, 20.6 mmol). Stir the reaction at room temperature for 1 hour then dilute with ethyl acetate (300 mL). Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL), then dry over anhydrous magnesium sulfate. After filtering, concentrate the solution under vacuum to dryness. Add dimethylformamide (250 mL) to the residue and cool in an ice bath before treating with carbon tetrabromide (12.78 g, 38.5 mmol) and triphenylphosphine (10.11 g, 38.5 mmol) for 3 hours. Add ethyl acetate (300 mL) and wash with water (2×200 mL) then saturated sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate and concentrate under vacuum. Purify the crude product via silica gel chromatography eluting with hexanes to afford 6.02 g (74%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H, J=1.9 Hz), 7.68 (dd, 1H, J=1.9 Hz, J=8.3 Hz), 7.47 (d, 1H, J=8.3 Hz), 4.57 (s, 2H). Treat the reaction at room temperature for 1 hour Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL) dry over anhydrous magnesium sulfate After filtering concentrate the solution under vacuum to dryness Add dimethylformamide (250 mL) to the residue and cool in an ice bath Add ethyl acetate (300 mL) and wash with water (2×200 mL) Dry over anhydrous magnesium sulfate concentrate under vacuum Purify the crude product via silica gel chromatography eluting with hexanes

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

Procedure: Treat a mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (6.52 g, 25.8 mmol) and methanol (250 mL) in a 500 mL flask with sodium borohydride (778 mg, 20.6 mmol). Stir the reaction at room temperature for 1 hour then dilute with ethyl acetate (300 mL). Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL), then dry over anhydrous magnesium sulfate. After filtering, concentrate the solution under vacuum to dryness. Add dimethylformamide (250 mL) to the residue and cool in an ice bath before treating with carbon tetrabromide (12.78 g, 38.5 mmol) and triphenylphosphine (10.11 g, 38.5 mmol) for 3 hours. Add ethyl acetate (300 mL) and wash with water (2×200 mL) then saturated sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate and concentrate under vacuum. Purify the crude product via silica gel chromatography eluting with hexanes to afford 6.02 g (74%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H, J=1.9 Hz), 7.68 (dd, 1H, J=1.9 Hz, J=8.3 Hz), 7.47 (d, 1H, J=8.3 Hz), 4.57 (s, 2H). Treat the reaction at room temperature for 1 hour Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL) dry over anhydrous magnesium sulfate After filtering concentrate the solution under vacuum to dryness Add dimethylformamide (250 mL) to the residue and cool in an ice bath Add ethyl acetate (300 mL) and wash with water (2×200 mL) Dry over anhydrous magnesium sulfate concentrate under vacuum Purify the crude product via silica gel chromatography eluting with hexanes

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

Procedure: Combine 4-bromo-1-(dibromomethyl)-2-(trifluoromethyl)benzene (6.66 g, 16.8 mmol), silver nitrate (14.8 g, 87.3 mmol), THF (250 mL), and water (35 mL) in a 500 mL flask equipped with a magnetic stir bar, reflux condenser, and N2 inlet. Reflux the mixture while stirring for 2.5 hours then cool to room temperature. Filter the reaction through Celite®, add ethyl acetate (250 mL) and wash with water (2×200 mL) then saturated aqueous sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate, concentrate to an orange oil, and purify the crude product via silica gel chromatography eluting with hexanes to afford 3.46 g (81%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 10.35-10.33 (m, 1H), 8.0 (d, 1H, J=8.3 Hz), 7.93 (d, 1H, J=1.4 Hz), 7.86 (dd, 1H, J=1.2 Hz, J=8.3 Hz). reflux condenser, and N2 inlet Reflux the mixture Filter the reaction through Celite® wash with water (2×200 mL) Dry over anhydrous magnesium sulfate concentrate to an orange oil purify the crude product via silica gel chromatography eluting with hexanes

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (9 g), 2-cyano-phenylboric acid (9.5 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (2.9 g), tetrabutylammonium bromide (1.15 g), 2M aqueous sodium carbonate solution (30 mL) and toluene (100 mL) was stirred at 100° C. overnight under an argon atmosphere. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (3.2 g, 32%). washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir: