4-bromo-3,5-difluoroaniline

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: To a solution of the 4-bromo-3,5-difluoroaniline (5 g, 20 mmol) in acetic acid (60 mL) was added NIS (5.68 g). The reaction mixture was stirred at room temperature for two hours, and poured into water (300 mL). The product was extracted with ethyl acetate (2×200 mL), and the combined organic layers were washed with 1N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The oily residue was filtered through a plug of silica gel, eluting with heptane/ethyl acetate (4:1). The filtrate was concentrated in vacuo to give the title compound (7.34 g) as a white solid. 1H NMR (500 MHz, CDCl3) δ 6.44 (dd, J=10.00, 1.95 Hz, 1H) 4.46 (br. s., 2H). The product was extracted with ethyl acetate (2×200 mL) the combined organic layers were washed with 1N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo The oily residue was filtered through a plug of silica gel eluting with heptane/ethyl acetate (4:1) The filtrate was concentrated in vacuo

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

Procedure: To a solution of the 4-bromo-3,5-difluoroaniline (5 g, 20 mmol) in acetic acid (60 mL) was added NIS (5.68 g). The reaction mixture was stirred at room temperature for two hours, and poured into water (300 mL). The product was extracted with ethyl acetate (2×200 mL), and the combined organic layers were washed with 1 N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The oily residue was filtered through a plug of silica gel, eluting with heptane/ethyl acetate (4:1). The filtrate was concentrated in vacuo to give the title compound (7.34 g) as a white solid. 1H NMR (500 MHz, CDCl3) δ 6.44 (dd, J=10.00, 1.95 Hz, 1 H) 4.46 (br. s., 2 H). The product was extracted with ethyl acetate (2×200 mL) the combined organic layers were washed with 1 N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo The oily residue was filtered through a plug of silica gel eluting with heptane/ethyl acetate (4:1) The filtrate was concentrated in vacuo

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

Procedure: A mixture of 4-bromo-3,5-difluoro-phenylamine (6.0 g, 28.8 mmole), ferrous sulfate (1.82 g), glycerol (8.6 mL), nitrobenzene (1.79 mL) and 5.0 ml of concentrated sulfuric acid (5 mL) was heated gently. After the first vigorous reaction, the mixture was heated to reflux for five hours. Nitrobenzene was removed by distillation in vacuo. The aqueous solution was acidified with glacial acetic acid, and dark brown precipitate separated, which was purified by flash chromatography (silica gel, petroleum/ethyl acetate=12/1) to return the title compound as a white solid (3.5 g, 49.8%). was heated gently After the first vigorous reaction the mixture was heated to reflux for five hours Nitrobenzene was removed by distillation in vacuo separated which was purified by flash chromatography (silica gel, petroleum/ethyl acetate=12/1)

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

Procedure: A mixture of 4-bromo-3,5-difluoro-phenylamine (6.0 g, 28.8 mmole), ferrous sulfate (1.82 g), glycerol (8.6 mL), nitrobenzene (1.79 mL) and 5.0 ml of concentrated sulfuric acid (5 mL) was heated gently. After the first vigorous reaction, the mixture was heated to reflux for five hours. Nitrobenzene was removed by distillation in vacuo. The aqueous solution was acidified with glacial acetic acid, and dark brown precipitate separated, which was purified by flash chromatography (silica gel, petroleum/ethyl acetate=12/1) to return the title compound as a white solid (3.5 g, 49.8%). was heated gently After the first vigorous reaction the mixture was heated to reflux for five hours Nitrobenzene was removed by distillation in vacuo separated which was purified by flash chromatography (silica gel, petroleum/ethyl acetate=12/1)

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

Procedure: To a solution of the 4-bromo-3,5-difluoroaniline (5 g, 20 mmol) in acetic acid (60 mL) was added NIS (5.68 g). The reaction mixture was stirred at room temperature for two hours, and poured into water (300 mL). The product was extracted with ethyl acetate (2×200 mL), and the combined organic layers were washed with 1N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The oily residue was filtered through a plug of silica gel, eluting with heptane/ethyl acetate (4:1). The filtrate was concentrated in vacuo to give the title compound (7.34 g) as a white solid. 1H NMR (500 MHz, CDCl3) δ 6.44 (dd, J=10.00, 1.95 Hz, 1H) 4.46 (br. s., 2H). The product was extracted with ethyl acetate (2×200 mL) the combined organic layers were washed with 1N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo The oily residue was filtered through a plug of silica gel eluting with heptane/ethyl acetate (4:1) The filtrate was concentrated in vacuo

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

Procedure: To a solution of the 4-bromo-3,5-difluoroaniline (5 g, 20 mmol) in acetic acid (60 mL) was added NIS (5.68 g). The reaction mixture was stirred at room temperature for two hours, and poured into water (300 mL). The product was extracted with ethyl acetate (2×200 mL), and the combined organic layers were washed with 1N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The oily residue was filtered through a plug of silica gel, eluting with heptane/ethyl acetate (4:1). The filtrate was concentrated in vacuo to give the title compound (7.34 g) as a white solid. 1H NMR (500 MHz, CDCl3) δ 6.44 (dd, J=10.00, 1.95 Hz, 1H) 4.46 (br. s., 2H). The product was extracted with ethyl acetate (2×200 mL) the combined organic layers were washed with 1N aqueous NaOH (200 mL) and saturated aqueous sodium thiosulfate (100 mL) The organic layer was dried over sodium sulfate filtered concentrated in vacuo The oily residue was filtered through a plug of silica gel eluting with heptane/ethyl acetate (4:1) The filtrate was concentrated in vacuo

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: The title compound (172 mg) was prepared from 4-bromo-3,5-difluoroaniline (200 mg, 1 mmol) and 3-butoxyphenyl boronic acid (242 mg, 1.2 mmol) as a colourless liquid.

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

Procedure: The title compound (500 mg) was prepared from 4-bromo-3,5-difluoroaniline (300 mg, 1.74 mmol) and 3-(ethylthio)phenylboronic acid (340 mg, 1.86 mmol) as a yellow liquid.