3-methoxy-2-nitrobenzonitrile → 2-Amino-3-methoxybenzonitrile

Participants

Reaction Steps

3-Methoxy-2-nitrobenzonitrile (Step 1, 43.3 g, 243 mmol) was suspended in AcOH (1000 mL) and degassed thoroughly. To this was added iron powder (40.7 g, 729 mmol) slowly. After 30 min an exotherm was observed and moderated by the use of an ice bath. After 2 h Celite was added and the entire mixture filtered through a pad of Celite. The Celite was washed well with AcOH, and the combined filtrates concentrated under reduced pressure to approximate volume of 100 mL AcOH. The residue was diluted with EtOAc (1000 mL), solid K2CO3 added and the mixture stirred overnight. The mixture was then filtered through Celite again and washed well with EtOAc. The solvent was removed under reduced pressure until a volume of approximately 500 mL EtOAc. This solution was washed with a saturated NaHCO3 solution (500 mL) and brine (300 mL) then the solvent removed under reduced pressure. The resulting solid was purified via silica gel chromatography (0-30% EtOAc/Hexanes). Fractions containing product were combined, the solvent removed under reduced pressure to give the title compound (26.6 g, 74%): HPLC MS RT=2.19 min, MH+=149.0; 1H NMR (DMSO-d6) δ: 3.77 (3H, s), 5.61 (2H, bs), 6.57 (1H, t), 6.96 (1H, dd), 7.00 (1H, dd).

Provenance & Evidence