2-chloro-6-fluoro-4-iodoaniline

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

Procedure: 2-Fluoro-4-iodo-6-chloroaniline (8.0 g, 36.0 mmol) is dissolved in DMF (110 mL) and treated with 2.8 equivalents of phenylboronic acid (10.0 g, 82 mmol), and a catalytic amount of tetrakistriphenylphosphine palladium(0) (3.0 g, 2.6 mmol) as a solution in DMF (20 mL). Sodium carbonate (30 mL of 2 M aqueous solution) is added and the reaction mixture stirred and heated to 100° C. for 24 hours. After cooling to room temperature most of the DMF is removed by rotary evaporator under high vacuum. The residual brown oil is partitioned between Et2O (300 mL) and water (150 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-fluoro-4-phenyl-6-chloroaniline (m.p. 105–107° C.). is removed by rotary evaporator under high vacuum The residual brown oil is partitioned between Et2O (300 mL) and water (150 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:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Fluoro-6-chloroaniline (28.8 g, 0.2 mol) is suspended in a solution of sodium bicarbonate (17.2 g, 0.2 mol in 150 mL water) and warmed to 60° C. Elemental iodine (50.8 g, 0.2 mol) is added portionwise and the resulting mixture stirred at 60° C. for 3 days. After cooling to room temperature, the reaction mixture is partitioned between CH2Cl2 (350 mL) and saturated sodium bisulfite solution (500 mL). The aqueous layer is re-extracted with additional CH2Cl2 (250 mL) and the combined organic layers dried (MgSO4) and concentrated by rotary evaporator. The residual oil is purified by flash chromatography (9:1 hexanes/EtOAc) to give 2-fluoro-4-iodo-6-chloroaniline (m.p. 85–87° C.). After cooling to room temperature the reaction mixture is partitioned between CH2Cl2 (350 mL) and saturated sodium bisulfite solution (500 mL) The aqueous layer is re-extracted with additional CH2Cl2 (250 mL) the combined organic layers dried (MgSO4) concentrated by rotary evaporator The residual oil is purified by flash chromatography (9:1 hexanes/EtOAc)