1,2-dibromo-5-fluoro-3-methylbenzene

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

Procedure: A solution of 2-bromo-4-fluoro-6-methylaniline HCl (5.0 g, 17.6 mmol) in 25% aq. HBr (38.1 mL, 175 mmol) was cooled to 0° C. and an aq. solution of sodium nitrite (0.59 mL, 18.4 mmol) added, followed by a small amount of EtOH to aid solubility. The reaction was stirred at this temperature for 25 min before transferring by pipette to a solution of copper(I) bromide (2.64 g, 18.4 mmol) in 25% aq. HBr (20 ml) at 70° C. The reaction was stirred at this temperature for 3 h. The reaction was quenched with NaHCO3 and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography (0-10% Hexene/EtOAC) to yield 1,2-dibromo-5-fluoro-3-methylbenzene as a clear oil. The reaction was stirred at this temperature for 3 h The reaction was quenched with NaHCO3 the aqueous layer was extracted with EtOAc The organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo The crude material was purified by column chromatography (0-10% Hexene/EtOAC)

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

Procedure: A solution of 2-bromo-4-fluoro-6-methylaniline HCl (5.0 g, 17.6 mmol) in 25% aq. HBr (38.1 mL, 175 mmol) was cooled to 0° C. and an aq. solution of sodium nitrite (0.59 mL, 18.4 mmol) added, followed by a small amount of EtOH to aid solubility. The reaction was stirred at this temperature for 25 min before transferring by pipette to a solution of copper(I) bromide (2.64 g, 18.4 mmol) in 25% aq. HBr (20 ml) at 70° C. The reaction was stirred at this temperature for 3 h. The reaction was quenched with NaHCO3 and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography (0-10% Hexene/EtOAC) to yield 1,2-dibromo-5-fluoro-3-methylbenzene as a clear oil. The reaction was stirred at this temperature for 3 h The reaction was quenched with NaHCO3 the aqueous layer was extracted with EtOAc The organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo The crude material was purified by column chromatography (0-10% Hexene/EtOAC)

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

Procedure: A solution of 2-bromo-4-fluoro-6-methylaniline HCl (5.0 g, 17.6 mmol) in 25% aq. HBr (38.1 mL, 175 mmol) was cooled to 0° C. and an aq. solution of sodium nitrite (0.59 mL, 18.4 mmol) added, followed by a small amount of EtOH to aid solubility. The reaction was stirred at this temperature for 25 min before transferring by pipette to a solution of copper(I) bromide (2.64 g, 18.4 mmol) in 25% aq. HBr (20 ml) at 70° C. The reaction was stirred at this temperature for 3 h. The reaction was quenched with NaHCO3 and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography (0-10% Hexene/EtOAC) to yield 1,2-dibromo-5-fluoro-3-methylbenzene as a clear oil. The reaction was stirred at this temperature for 3 h The reaction was quenched with NaHCO3 the aqueous layer was extracted with EtOAc The organic layer was then washed with water and brine (3× ea.) dried over Na2SO4 concentrated in vacuo The crude material was purified by column chromatography (0-10% Hexene/EtOAC)