Methyl Acetate → 1-(Pyridin-3-yl)butane-1,3-dione

To a solution of 1-(3-pyridyl)ethanone (15.0 g, 124 mmol) in DMF (100 mL) at 0° C. was added sodium hydride (5.9 g, 149 mmol). The reaction mixture was then stirred at room temperature for 10 minutes. After cooling to 0° C., methyl acetate (11.8 mL, 149 mmol) was slowly added dropwise. The reaction mixture was allowed to slowly warm to room temperature and stirred overnight. The reaction mixture was quenched with the addition of saturated ammonium chloride (100 mL) and acidified to pH 5 with the addition of 1 N HCl. The mixture was then extracted with ethyl acetate (2×75 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The 16 grams of crude product were filtered through a plug of silica gel. The filtrate was concentrated under reduced pressure. The residue was taken up in a 1:9 solution of ethyl acetate/hexane (300 mL) at 65° C. The resulting solution was slowly allowed to cool to warm temperature while stirring. The precipitate was collected by vacuum filtration to provide 1-(3-pyridyl)butane-1,3-dione (7.7 g) as a yellow solid.

1. temperatureAfter cooling to 0° C.
2. temperatureto slowly warm to room temperature
3. stirringstirred overnight
4. customThe reaction mixture was quenched with the addition of saturated ammonium chloride (100 mL)
5. additionacidified to pH 5 with the addition of 1 N HCl
6. extractionThe mixture was then extracted with ethyl acetate (2×75 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. filtrationThe 16 grams of crude product were filtered through a plug of silica gel
11. concentrationThe filtrate was concentrated under reduced pressure
12. customwas taken up in a 1:9 solution of ethyl acetate/hexane (300 mL) at 65° C
13. temperatureto cool
14. temperatureto warm temperature
15. stirringwhile stirring
16. filtrationThe precipitate was collected by vacuum filtration

ORD record

ord-b721fa7df8c147269dfdc994e1d2e115

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403839B2