4-bromo-2,3,5,6-tetrafluoroaniline

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

Procedure: A mixture of 4,4,5,5-tetramethyl-2-(4-octylphenyl)-1,3,2-dioxaborolane (415.0 mg, 1.31 mmol), 4-bromo-2,3,5,6-tetrafluorobenzenamine (213.0 mg, 0.87 mmol), and a quaternary ammonium salt (Aliquat 336, 0.090 g) was degassed three times with nitrogen before dry toluene (7.0 mL) was added. This step was followed by addition of tetrakis(triphenylphosphine) palladium (100.0 mg) and sodium carbonate (aq. 1 M, 4.0 mL), which had been deaerated for 2 hour, under nitrogen. The mixture was stirred vigorously, and heated at reflux for 20 hours. The organic phase of the resulting reaction mixture was filtered through a thin layer of Celite® and evaporated to dryness to give 0.6 g of a crude product. The crude material was purified by chromatography on silica gel (by using ethyl acetate:hexanes (1:9) as the eluent) to yield 2,3,5,6-tetrafluoro-4′-octylbiphenyl-4-amine as an off-white solid (0.280 g, 91% yield). a quaternary ammonium salt (Aliquat 336, 0.090 g) was degassed three times with nitrogen before dry toluene (7.0 mL) was added This step was followed by addition of tetrakis(triphenylphosphine) palladium (100.0 mg) and sodium carbonate (aq. 1 M, 4.0 mL), which heated at reflux for 20 hours The organic phase of the resulting reaction mixture was filtered through a thin layer of Celite® evaporated to dryness to give 0.6 g of a crude product The crude material was purified by chromatography on silica gel (

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

Procedure: The title compound (250 mg) was prepared from 4-bromo-2,3,5,6-tetrafluoroaniline (300 mg, 1.23 mmol) and 3-butoxyphenylboronic acid (310 mg, 1.59 mmol) as a yellow liquid.

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

Procedure: The title compound (280 mg) was prepared from 4-bromo-2,3,5,6-tetrafluoroaniline (300 mg, 1.22 mmol) and 3-(ethylthio)phenylboronic acid (291 mg, 1.6 mmol) as a colourless liquid.

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

Procedure: The title compound (280 mg) was prepared from 4-bromo-2,3,5,6-tetrafluoroaniline (300 mg, 1.22 mmol) and 3-(ethylthio)phenylboronic acid (291 mg, 1.6 mmol) as a colourless liquid.

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Alternative procedure: 2,3,5,6-Tetrafluoro-4-bromoaniline (12.0 g, 49.2 mmol) is dissolved in DME (250 mL) and treated with 3-methoxyphenylboronic acid (7.5 g, 49.2 mmol), a catalytic amount of palladium(II) acetate (0.23 g, 1.0 mmol) and tri-o-tolylphosphine (1.22 g, 4.0 mmol). Potassium carbonate (13.6 g in 50 mL water) is added and the reaction mixture stirred, purged with nitrogen, then heated to 90° C. for 24 hours. After cooling to room temperature most of the DME is removed by rotary evaporator under high vacuum. The resulting material is partitioned between EtOAc (200 mL) and water (250 mL). The organic layer is washed with brine, dried (Na2SO4) and concentrated by rotary evaporator. The crude reaction product is purified by flash chromatography (9:1 hexanes/EtOAc, then 6:4 hexanes/EtOAc) to give 2,3,5,6-tetrafluoro-4-(3′-methoxyphenyl)aniline (m.p. 94–96° C.). purged with nitrogen After cooling to room temperature most of the DME is removed by rotary evaporator under high vacuum The resulting material is partitioned between EtOAc (200 mL) and water (250 mL) The organic layer is washed with brine dried (Na2SO4) concentrated by rotary evaporator The crude reaction product is purified by flash chromatography (9:1 hexanes/EtOAc

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,3,5,6-Tetrafluoro-4-bromoaniline (7.5 g, 30.7 mmol) is dissolved in DME (150 mL) and treated with 3-methoxyphenylboronic acid (4.7 g, 30.7 mmol), a catalytic amount of tetrakistriphenylphosphine palladium(0) (0.70 g, 0.6 mmol) and triphenylphosphine (0.66 g, 2.5 mmol). Potassium carbonate (8.5 μg in 50 mL of water) is added and the reaction mixture stirred and heated to 90° C. for 24 hours. After cooling to room temperature most of the DME is removed by rotary evaporator under high vacuum. The resulting material is partitioned between EtOAc (200 mL) and water (250 mL). The organic layer is washed with brine, dried (Na2SO4) and concentrated by rotary evaporator. The crude reaction product is purified by flash chromatography (9:1 hexanes/EtOAc, then 6:4 hexanes/EtOAC) to give 2,3,5,6-tetrafluoro-4-(3′-methoxyphenyl)aniline (m.p. 94–96° C.). is removed by rotary evaporator under high vacuum The resulting material is partitioned between EtOAc (200 mL) and water (250 mL) The organic layer is washed with brine dried (Na2SO4) concentrated by rotary evaporator The crude reaction product is purified by flash chromatography (9:1 hexanes/EtOAc

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

Procedure: 2,3,5,6-Tetrafluoro-4-bromoaniline (13.8 g, 56.7 mmol) is dissolved in benzene (200 mL) and treated with 1.5 equivalents of phenylboronic acid (10.4 g, 85.1 mmol) and a catalytic amount of tetrakistriphenylphosphine palladium(0) (4.2 g, 3.6 mmol) as a solution in ethanol (30 mL). Sodium carbonate (60 mL of 2 M aqueous solution) is added and the reaction mixture stirred and heated to reflux temperature for 24 hours. After cooling to room temperature the mixture is partitioned between Et2O (500 mL) and water (250 mL). The organic layer is washed with brine, dried (MgSO4) and concentrated by rotary evaporator. The residual oil is purified by flash chromatography (9:1 hexanes/EtOAc) to give 2,3,5,6-tetrafluoro-4-phenylaniline as an oil. heated to reflux temperature for 24 hours is partitioned between Et2O (500 mL) and water (250 mL) The organic layer is washed with brine dried (MgSO4) concentrated by rotary evaporator The residual oil is purified by flash chromatography (9:1 hexanes/EtOAc)

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

Procedure: 2,3,5,6-Tetrafluoroaniline (25.0 g, 0.15 mol) is dissolved in methanol (100 mL) and treated with elemental bromine (28.4 g, 0.17 mol) by dropwise addition at room temperature. Solid sodium bicarbonate (15 g, 0.18 mol) is added portionwise and the resulting mixture stirred for an additional 2 hours. The reaction mixture is partitioned between Et2O (500 mL) and water (1000 mL). The organic layer is dried (MgSO4) and evaporated by a rotary evaporator to give 2,3,5,6-tetrafluoro-4-bromoaniline (m.p. 59–60° C.). The reaction mixture is partitioned between Et2O (500 mL) and water (1000 mL) The organic layer is dried (MgSO4) evaporated by a rotary evaporator

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

Procedure: A mixture of 4,4,5,5-tetramethyl-2-(4-octylphenyl)-1,3,2-dioxaborolane (415.0 mg, 1.31 mmol), 4-bromo-2,3,5,6-tetrafluorobenzenamine (213.0 mg, 0.87 mmol), and a quaternary ammonium salt (Aliquat 336, 0.090 g) was degassed three times with nitrogen before dry toluene (7.0 mL) was added. This step was followed by addition of tetrakis(triphenylphosphine) palladium (100.0 mg) and sodium carbonate (aq. 1 M, 4.0 mL), which had been deaerated for 2 hour, under nitrogen. The mixture was stirred vigorously, and heated at reflux for 20 hours. The organic phase of the resulting reaction mixture was filtered through a thin layer of Celite® and evaporated to dryness to give 0.6 g of a crude product. The crude material was purified by chromatography on silica gel (by using ethyl acetate:hexanes (1:9) as the eluent) to yield 2,3,5,6-tetrafluoro-4′-octylbiphenyl-4-amine as an off-white solid (0.280 g, 91% yield). a quaternary ammonium salt (Aliquat 336, 0.090 g) was degassed three times with nitrogen before dry toluene (7.0 mL) was added This step was followed by addition of tetrakis(triphenylphosphine) palladium (100.0 mg) and sodium carbonate (aq. 1 M, 4.0 mL), which heated at reflux for 20 hours The organic phase of the resulting reaction mixture was filtered through a thin layer of Celite® evaporated to dryness to give 0.6 g of a crude product The crude material was purified by chromatography on silica gel (