4-bromo-2-fluoro-6-methylaniline

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: Pivaloyl chloride (4 mL, 38.4 mmol) was added slowly (caution—exothermic reaction) to an ice cold solution of the crude 4-bromo-2-fluoro-6-methylaniline from step 4 (about 32 mmol) in pyridine (20 mL). After the addition, the ice bath was removed and the warm reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into a water solution of 1 N HCl and extracted with EtOAc. The organic layer was washed with 1N HCl three times, dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography on a Biotage 40M KP-Sil column, eluting with 9:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide N-(4-bromo-2-fluoro-6-methylphenyl)-2,2-dimethylpropanamide (4.3 g, 49% for 3 steps) as a yellow solid. After the addition the ice bath was removed the warm reaction mixture extracted with EtOAc The organic layer was washed with 1N HCl three times dried over MgSO4 filtered concentrated under vacuum The residue was purified by flash chromatography on a Biotage 40M KP-Sil column eluting with 9:1 hexanes-EtOAc The product containing fractions were evaporated under vacuum

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

Procedure: A solution of crude 2-fluoro-6-methylaniline from step 3 (about 32 mmol) in anhydrous N,N-dimethylformamide (100 mL) was cooled in an ice bath, placed under a nitrogen atmosphere, treated with N-bromosuccinimide (5.7 g, 32 mmol), and then stirred at room temperature for 10 minutes. The reaction mixture was poured into a water solution of diluted brine and extracted with EtOAc. The organic extracts were washed with diluted brine three times, dried over MgSO4, filtered through a pad of silica, and concentrated under vacuum to afford 4-bromo-2-fluoro-6-methylaniline as a yellow foam. extracted with EtOAc The organic extracts were washed with diluted brine three times dried over MgSO4 filtered through a pad of silica concentrated under vacuum