Bromine → 4-Bromo-3-fluoro-2-methoxyaniline

Participants

Reaction Steps

To a solution of 2-methoxy-3-fluoroaniline (Compound 147I, 7.70 g, 54.6 mmol) in AcOH (45.0 mL) was added a solution of bromine (6.98 g, 43.6 mmol) in AcOH (45.0 mL) dropwise. The reaction mixture was stirred at rt for 30 minutes. The resulting solid was filtered and washed with acetic acid to give the HBr salt of the desired product. The solid was dissolved in water (15 mL), basified by addition of KOH, and extracted with EtOAc (20 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give a white solid. The crude material was purified by silica gel chromatography on an ISCO combi-flash Rf system using Heptane/EtOAc (100:0→70:30) as eluent to yield the desired product as a white solid, 6.536 mg (54% yield). 1H NMR (CDCl3, 400 MHz): δ=3.93 (d, J=1.52 Hz, 3 H), 6.42 (dd, J=8.84, 1.77 Hz, 1 H), 7.01 (dd, J=8.72, 6.95 Hz, 1 H). MS (ES+): m/z 221.98 [MH+] (TOF, polar).

Provenance & Evidence