Water → 5-Methoxy-2-methylpyridine

Participants

Reaction Steps

6-methylpyridin-3-ol (50.0 g, 0.458 mol) was added to a suspension of powdered KOH (103 g, 1.83 mol) in dimethylsulfoxide (750 mL) and the mixture was left to stir at room temperature under nitrogen for 1.5 hours. Methyl iodide (30 mL, 68.3 g, 0.481 mol) was then added dropwise over 1 hour to the dark brown mixture (exothermic). After stirring at room temperature for 1.5 hours water (1.0 L) was added and the mixture was extracted with ethyl acetate (2×300 mL). The combined organic extracts were washed with brine, dried (MgSO4) and evaporated at 40° C. on a rotary evaporator. The residue was purified by column chromatography (silica), eluting with pentane, increasing polarity to ethyl acetate, to give the volatile product as a ˜1:1 mixture with ethyl acetate (40 g, ˜23.3 g product, 41%). 1H NMR (CDCl3, 400 MHz) δ 2.45 (3H, s), 3.79 (3H, s), 7.02 (1H, d), 7.08 (1H, dd), 8.16 (1H, d).

Provenance & Evidence