Pyridine → HCID 11629954, compound

Participants

Reaction Conditions

Reaction Steps

Acetyl chloride (121 μL, 1.70 mmol) is added drop-wise to a mixture of 5-ethyl-N-hydroxy-6-methoxy-2-methylnicotinamidine (formed on 1.705 mmol scale) in pyridine (5 mL) under a nitrogen atmosphere. After the vigorous reaction has ceased, the mixture is heated at 98° C. for 22 hr. LC/MS indicates the reaction is incomplete and a further amount of acetyl chloride (50 μL) is added and the reaction mixture is heated for an additional 40 min. The reaction mixture is allowed to cool, then evaporated to dryness. The residue is suspended in water and extracted with three portions of ethyl acetate. The combined ethyl acetate layer is washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and evaporated to leave a sticky, orange residue. The residue is extracted with five portions of heptane and the combined extract is evaporated. The residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with heptane:dichloromethane (9:1, increasing to 4:1). Clean fractions containing the product are combined and the solvent evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(5-methyl-1,2,4-oxadiazol-3-yl)pyridine (47 mg, 20% combined yield from Steps 3 and 4) as an off-white solid. MS: m/e=234 (M+H); 1H NMR (CDCl3, δ, ppm): 7.94 (1H, s), 4.00 (3H, s), 2.74 (3H, s), 2.64 (3H, s), 2.60 (2H, q), 1.10 (3H, t).

Provenance & Evidence