Dimethylformamide → 6-amino-3-bromo-2-fluoro-N-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

NBS (9.42 g, 52.9 mmol) was added to a cold (0° C.) solution of 5-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (Compound 27E, 9.2 g, 50.8 mmol) in DCM and DMF (120 mL+60 mL) over the course of 40 min. The reaction mixture was stirred at 0° C. for 2 h then allowed to warm to RT. After 30 min, the DCM was removed in vacuo. The remaining reaction mixture was cooled −10° C., treated with a solution of 2M methyl amine in THF (50.8 mL, 101.6 mmol) and allowed to stir for overnight at room temperature. The reaction mixture was poured to water (240 mL) and the resulting suspension was extracted with ethyl acetate (3×100 mL). The combined ethyl acetate layer was washed with water (3×100 mL), dried (Na2SO4) and concentrated to give crude residue which was purified by column chromatography (20% ethyl acetate/hexanes) to afford 4 g of the title compound (32% over two steps). 1H NMR (CDCl3, 500 MHz) δ=2.98 (d, J=4.5 Hz, 3H), 5.90 (brs, 2H), 6.38 (d, J=9.0 Hz, 1H), 6.55 (brs, 1H), 7.24-7.27 (m, 1H).

Provenance & Evidence