Dimethylformamide → 2-Fluoro-6-nitroanisole

Participants

Reaction Conditions

Reaction Steps

Potassium carbonate (59.25 g, 0.43 mol) is added slowly to a solution of dimethylformamide (200 mL) containing 2-fluoro-6-nitrophenol (10, 33.63 g, 0.21 mol) and dimethylsulfate (41.0 mL, 0.43 mol) at room temperature. The orange mixture is stirred at 80° C. for 6 h. The resulting yellow mixture is cooled to room temperature, diluted with water (500 mL), and extracted with hexanes (3×500 mL). The combined organic extracts are dried over magnesium sulfate and evaporated under reduced pressure to give 1-fluoro-2-methoxy-3-nitrobenzene as a yellow oil. This product is of sufficient purity (≧95% by NMR spectroscopy) to use directly in the next synthetic step. 1H NMR (CDCl3): δ 4.08 (d, JH-F=2.0 Hz, 3H, OCH3), 7.13 (apparent t of d, JH-H=8.5 Hz, JH-F=5.0 Hz, 1H, H-5), 7.34 (d, JH-F=10.5 Hz, JH-H=8.5 Hz, JH-H=1.5 Hz, 1H, H-6), 7.58 (d of apparent t, JH-H=8.5 Hz, JH-H=1.5 Hz, JH-F=1.5 Hz, 1H, H-4). 19F{1H} NMR (CDCl3): 8-126.7 (s). 13C{1H} NMR (CDCl3): δ 62.6 (d, JC-F=5.5 Hz, OCH3), 120.2 (d, JC-F=3.5 Hz, C-4), 121.1 (d, JC-F=19.5 Hz, C-6), 123.2 (d, JC-F=8.0 Hz, C-5), 142.2 (d, JC-F=14.5 Hz, C-2), 144.8 (br, C-3), 156.2 (d, JC-F=251.5 Hz, C-1). LCMS m/z calcd for C7H6FNO3 ([M]+) 171. Found 183 ([M−CH2O+H+ CH3CN]+, 26%), 183 ([M-CH2O+H]+, 100%).

Provenance & Evidence