4-bromo-5-fluoro-2-iodoaniline

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: Triethylamine (44 mL) followed by trimethylsilylacetylene (0.737 mL, 5.32 mmol) were added dropwise to a suspension of 4-bromo-5-fluoro-2-iodoaniline (1.4 g, 4.43 mmol), Pd(PPh3)2Cl2 (0.156 g, 0.222 mmol), and CuI (0.042 g, 0.222 mmol) at 0° C. The reaction was warmed to ambient temperature and stirred for 2 h. The reaction was concentrated, diluted with Et2O, and filtered through Celite. The filtrate was washed with brine, dried (Na2SO4), filtered and concentrated. Chromatography over silica eluting with 2-8% EtOAc/hexanes afforded the desired product as a yellow oil. The reaction was concentrated diluted with Et2O filtered through Celite The filtrate was washed with brine dried (Na2SO4) filtered concentrated

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

Procedure: N-iodosuccinimide (2.90 ml, 28.9 mmol) was added to a solution of 4-bromo-3-fluoroaniline (5.00 g, 26.3 mmol) in AcOH (52.6 ml). The reaction was maintained at ambient temperature for 1.5 h, then diluted with 20 mL toluene and concentrated. The residue was dissolved in EtOAc and washed with 2 N aqueous NaOH. The organic phase was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 2-10% EtOAc/Heptane) to give 4-bromo-5-fluoro-2-iodoaniline (7.23 g, 22.89 mmol, 87% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.74-7.78 (m, 1H), 6.53-6.57 (m, 1H). m/z (ESI) 315.9 (M+H)+. concentrated The residue was dissolved in EtOAc washed with 2 N aqueous NaOH The organic phase was washed with brine dried over sodium sulfate filtered concentrated The residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 2-10% EtOAc/Heptane)

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

Procedure: To a vial was added, 4-bromo-5-fluoro-2-iodoaniline (5.67 g, 17.95 mmol), PdOAc2 (0.201 g, 0.897 mmol), sodium bicarbonate (3.77 g, 44.9 mmol), ethyl acrylate (2.049 ml, 18.85 mmol) and DMF (12.0 ml). The reaction was heated for 3 hour at 100° C. The reaction was cooled to RT, diluted with water and extracted with DCM (3×). The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The resulting material was triturated with heptane overnight and then filtered to afford (E)-ethyl 3-(2-amino-5-bromo-4-fluorophenyl)acrylate (4.00 g, 13.88 mmol, 77% yield) as a light yellow solid. m/z (ESI) 288.0 (M+H)+. To a vial was added The reaction was cooled to RT extracted with DCM (3×) The combined organics were washed with water and brine dried over magnesium sulfate filtered concentrated The resulting material was triturated with heptane overnight filtered