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

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.]

1. temperatureThe reaction mixture was heated at
2. temperaturea vigorous reflux with the aid of a heating mantle in a flask without a stir bar
3. customthe iron powder was removed by filtration through a pad of Celite
4. concentrationThe filtrate was concentrated
5. customthe residue was transferred to a separatory funnel
6. additioncontaining saturated aqueous NaHCO3 (50 ml)
7. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
8. washThe combined organic layers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by MPLC on silica gel (20%→50% ethyl acetate in hexanes)

ORD record

ord-6206956ff1974f04ae4a304693151262

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932256B2