2-(Difluoromethoxy)-3,6-dimethyl-5-nitropyridine → 6-(Difluoromethoxy)-2,5-dimethylpyridin-3-amine

Participants

Reaction Steps

Alternate route. To a solution of 2-(difluoromethoxy)-3,6-dimethyl-5-nitropyridine (1.00 g, 4.58 mmol) in EtOH (40 mL) and acetic acid (4 mL) was added iron powder (1.26 g, 22.9 mmol). The reaction mixture was heated at a vigorous reflux with the aid of a heating mantle in a flask without a stir bar. After 1.75 h, the reaction mixture was cooled to room temperature and the iron powder was removed by filtration through a pad of Celite. The filtrate was concentrated and the residue was transferred to a separatory funnel containing saturated aqueous NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by MPLC on silica gel (20%→50% ethyl acetate in hexanes) to afford 6-(difluoromethoxy)-2,5-dimethylpyridin-3-amine (774 mg, 90% yield) as a pale yellow solid identical to that prepared by Method A: mp 38.4-39.4° C.; 1H NMR (400 MHz, CDCl3) δ 7.35 (t, J=74.5 Hz, 1H), 6.82 (s, 1H), 2.26 (s, 3H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.6, 137.4, 137.1, 127.4, 119.0, 115.0 (J=251.3 Hz), 19.3, 14.8; LRMS (ESI) m/e 189.0 [(M+H)+, calcd for C8H11N2OF2 189.1].

Provenance & Evidence