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

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).

1. filtrationThe resulting solid was filtered
2. washwashed with acetic acid

ORD record

ord-f9e825b0199b443699a623d79eae85b4

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096624B2