反应详情

温度

90 °C

In a round bottom flask under a nitrogen atmosphere a mixture of N-dimethylaminomethylene-5-ethyl-6-methoxy-2-methylnicotinamide (synthesized on 1.13 mmol scale) of Step 2, Example 16, hydroxylamine hydrochloride (103 mg, 1.48 mmol) and sodium hydroxide (59.4 mg, 1.48 mmol) and glacial acetic acid (1.7 mL) is treated with water (0.85 mL) and 1,4-dioxane (1.24 mL). The resulting dark mixture is stirred at 90° C. for 45 min. The reaction mixture is evaporated and the residue is partitioned between water and dichloromethane. The mixture is treated with excess solid sodium bicarbonate, the dichloromethane layer is separated and the aqueous layer is extracted with 2 further portions of dichloromethane. The combined organic layer is dried over magnesium sulfate and evaporated. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined and the solvent evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(1,2,4-oxadiazol-5-yl)pyridine as a white solid (138 mg, 56% yield, 2 steps). NMR (CDCl3, δ ppm): 8.45 (1H, s), 8.05 (1H, s), 4.02 (3H, s), 2.82 (3H, s), 2.62 (2H, q), 1.23 (3H, t).

1. customThe reaction mixture is evaporated
2. customthe residue is partitioned between water and dichloromethane
3. additionThe mixture is treated with excess solid sodium bicarbonate
4. customthe dichloromethane layer is separated
5. extractionthe aqueous layer is extracted with 2 further portions of dichloromethane
6. dry with materialThe combined organic layer is dried over magnesium sulfate
7. customevaporated
8. customThe crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane
9. additionFractions containing the product
10. customevaporated
11. customre-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane
12. additionFractions containing the product
13. customthe solvent evaporated