Boron trifluoride etherate → HCID 67492215, compound

Participants

Reaction Conditions

Reaction Steps

To a crude mixture of 5-ethyl-N-hydroxy-6-methoxy-2-methylnicotinamidine (formed on 1.705 mmol scale following the procedures of Step 3, Example 22), under a nitrogen atmosphere, is added triethylorthoformate (2 mL), followed by boron trifluoride etherate (42.6 μL, 0.336 mmol). The resulting solution mixture is heated at 100° C. for 3.25 hr. The mixture is allowed to cool, concentrated under vacuum, then treated with aqueous hydrochloric acid (1M, 2 mL). The resulting mixture is allowed to stand for 30 min before making basic with excess solid sodium bicarbonate. The mixture is extracted with five portions of ethyl acetate, dried over magnesium sulfate, filtered and evaporated to leave an oily, brown residue that is purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (1:1, increasing to 4:1). Fractions containing the product are combined, the solvent evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (9:1, increasing to 17:3 then 1:1). Fractions containing the product are combined, the solvent evaporated and further purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (87:13, then 1:1). Clean fractions containing the product are combined, evaporated and triturated with heptane to give 3-ethyl-2-methoxy-6-methyl-5-(1,2,4-oxadiazol-3-yl)-pyridine (57 mg, 15% yield, 2 steps). MS: m/e=220 (M+H); 1H NMR (300 MHz, CDCl3, δ, ppm): 8.72 (1H, s), 7.99 (1H, s), 4.00 (3H, s), 2.76 (3H, s), 2.61 (2H, q), 1.11 (3H, t)

Provenance & Evidence