Pyridine, hydrofluoride (1:1) → 1-Fluoro-5-methoxy-2-methyl-4-nitrobenzene

Participants

Reaction Steps

Under nitrogen in a nalgene bottle, a stirring solution of pyridine (17.1 mL, 3.2 M, −70° C.) was treated dropwise with HF-pyridine (51.91 mL). Next, 5-methoxy-2-methyl-4-nitro-phenylamine (10.0 g, 54.9 mmol) was added followed by sodium nitrite (6.4 g, 92.76 mmol). The dry ice/acetone bath was removed and the reaction was allowed to warm to room temperature. The solution was then heated at 60° C. for 2 h (or until nitrogen evolution stops.) After cooling to room temperature, the nalgene bottle was placed in an ice bath and 375 mL of water was slowly added to the solution. The resulting orange precipitate was collected by suction filtration and washed with 250 mL of water. Purification of the solid via silica gel flash chromatography (30% ethyl acetate in heptane) provided 1-fluoro-5-methoxy-2-methyl-4-nitro-benzene (7.69 g, 76%) as a light orange solid: mp 71–74° C.; Rf 0.56 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 7.82 (d, J=7.5 Hz, 1 H), 6.75 (d, J=10.5 Hz, 1 H), 3.93 (s, 3 H), 2.25 (d, J=2.1 Hz, 3 H); ESI-LC/MS m/z calcd for C8H8FNO3: 185.1; Found 186.0 (M+1)+. Anal. calcd for C8H8FNO3: C, 51.90; H, 4.36. Found C, 52.11; H, 4.47.

Provenance & Evidence