4-bromo-2-fluoro-6-iodoaniline

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (4-bromo-2-fluoro-6-iodophenyl)amine (D159) (2 g), 4-pentynoic acid (0.62 g) and copper(I) iodide (0.60 g) in DMF (4 mL) stirred under nitrogen at room temperature was added bis(triphenylphosphine)palladium(II) chloride (0.222 g), then triethylamine (2.2 mL) was added in a portion. The reaction mixture was stirred at 80° C. in microwave reactor for 2 hrs. The solid in the mixture was filtered, the filtrate was diluted with EtOAc (30 mL), washed with brine (80 mL) and water (50 mL×2). The organic layer was dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford 3-(5-bromo-7-fluoro-1H-indol-2-yl)propanoic acid (D160) (700 mg) as a yellow solid. MS (ES): C11H9BrFNO2 requires 285; found 286.0 (M+H+). δH (CDCl3, 400 MHz): 2.75 (2H, t), 3.07 (2H, t), 5.45 (1H, s), 7.05 (1H, d), 7.41 (1H, s). The solid in the mixture was filtered the filtrate was diluted with EtOAc (30 mL) washed with brine (80 mL) and water (50 mL×2) The organic layer was dried over anhydrous sodium sulfate The dried solution was concentrated The residue was purified by column chromatography

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

Procedure: (4-bromo-2-fluorophenyl)amine (6 g) was dissolved in ethanol (200 mL), silver sulfate (10.8 g) was added and then iodine (8.8 g) was added in small portions. After the addition was complete, the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was filtered and evaporated to leave a dark oil which was taken up in EtOAc, washed with saturated sodium thiosulphate (100 mL×2), sodium carbonate solution (100 mL×2) and water. The organic layer dried over anhydrous Na2SO4 and evaporated. The crude product was purified by column chromatography to give (4-bromo-2-fluoro-6-iodophenyl)amine (D159) (8.6 g) as a yellow solid. MS (ES): C6H4BrFIN requires 315; found 315.9 (M+H+). After the addition The reaction mixture was filtered evaporated to leave a dark oil which washed with saturated sodium thiosulphate (100 mL×2), sodium carbonate solution (100 mL×2) and water The organic layer dried over anhydrous Na2SO4 evaporated The crude product was purified by column chromatography