2-CHLORO-3,5-DIBROMO-1-FLUOROBENZENE

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of but-3-enyl-carbamic acid benzyl ester (5.00 g, 24.36 mmol, 1 eq) in anhydrous toluene (60 mL) was cooled under argon to 0-5° C. 9-BBN (0.50 M, solution in THF; 54.6 mL, 26.80 mmol, 1.1 eq.) was added dropwise, and the mixture was allowed to reach room temperature. After 24 h, the resulting solution was added dropwise at room temperature to a mixture of 2a (7.03 g, 24.36 mmol, 1 eq.), 1N NaOH/H2O (40 mL, 40 mmol, 1.6 eq.), and toluene (20 mL). The mixture was then degassed with argon and Pd(PPh3)4 (1.13 g, 0.98 mmol, 0.04 eq.) was added. The mixture was rapidly stirred under argon at 60° C. for 24 h, before cooling to room temperature. The mixture was partitioned between EtOAc (150 mL) and brine (150 mL). The organic phase was washed with brine (200 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0-50% EtOAc in Heptane) to afford 3a as a colorless oil (3.54 g, 35%). to reach room temperature was added before cooling to room temperature The mixture was partitioned between EtOAc (150 mL) and brine (150 mL) The organic phase was washed with brine (200 mL) dried over Na2SO4 filtered concentrated The crude product was purified by flash chromatography on silica gel (0-50% EtOAc in Heptane)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,6-dibromo-3-chloro-4-fluoro-phenylamine (1a, 4.85 g, 16 mmol, 1 eq.) in DMF (20 mL) was added to a solution of isoamylnitrite (3.46 mL, 25.6 mmol, 1.6 eq.) in DMF (12 mL) at 70° C. The mixture was heated at 70° C. for 3 h before it was cooled to room temperature, quenched with 1 N NaOH aqueous solution (150 mL), and extracted with EtOAc (200 mL). The EtOAc extract was washed with brine (100 mL×2), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (heptane) to give desired product 2a as colorless oil (3.70 g, 80%). was cooled to room temperature quenched with 1 N NaOH aqueous solution (150 mL) extracted with EtOAc (200 mL) The EtOAc extract was washed with brine (100 mL×2) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (heptane)