反应详情

A dry 50 mL three neck flask fitted with a reflux condenser and internal thermometer was charged with dry methanol (20 mL). Sodium (516 mg, 0.022 mol) was added in portions and after all the sodium had dissolved the methanol was removed by distillation. The resulting sodium methoxide was cooled and a mixture of methyl-3-methoxyisonicotinoate (2.50 g, 0.015 mol) and methyl acetate (6.65 g, 0.090 mol) was added dropwise. The mixture was refluxed for four hours, allowed to cool and dissolved in water (9.0 mL) and concentrated hydrochloric acid (6.0 mL). The resulting mixture was heated to reflux for 2.5 hours, cooled, and basified with 5% sodium bicarbonate. The mixture was extracted with chloroform (4×50 mL) and the combined extracts dried over sodium sulfate, concentrated, and chromatographed through a short column of silica gel to afford 3-methoxy-4-acetylpyridine (1.05 g, 46%). mp. 36°-37° C.

1. customwas removed by distillation
2. temperatureThe resulting sodium methoxide was cooled
3. additionwas added dropwise
4. temperatureThe mixture was refluxed for four hours
5. temperatureto cool
6. temperatureThe resulting mixture was heated
7. temperatureto reflux for 2.5 hours
8. temperaturecooled
9. extractionThe mixture was extracted with chloroform (4×50 mL)
10. dry with materialthe combined extracts dried over sodium sulfate
11. concentrationconcentrated
12. customchromatographed through a short column of silica gel