2-Methylpyridine → 1-Cyclopentyl-2-(pyridin-2-yl)ethan-1-one

Temperature

-78 °C

A 100 mL round bottom flask was charged with 2-picoline (2.97 mL, 30.05 mmol) and anhydrous THF (30 mL). The solution was cooled to −78° C. and n-butyllithium (20.7 mL of a 1.6 M solution in THF, 33.1 mmol) was added dropwise. The reaction mixture was slowly warmed to room temperature and then stirred for one hour. The reaction mixture was then cooled back to −78° C. and N-methoxy-N-methyl-cyclopentyl amide (5.0 g, 31.85 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight with stirring and then quenched with 0.1 N HCL to pH 9. The mixture was then extracted with methylene chloride, the organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography (ethyl acetate:hexane, 3:7, silica gel) to provide 1-cyclopentyl-2-(2-pyridyl)ethan-1-one (4.35 g, 77%).

1. temperatureThe reaction mixture was slowly warmed to room temperature
2. temperatureThe reaction mixture was then cooled back to −78° C.
3. temperatureto warm to room temperature overnight
4. stirringwith stirring
5. customquenched with 0.1 N HCL to pH 9
6. extractionThe mixture was then extracted with methylene chloride
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customThe residue was purified by flash chromatography (ethyl acetate:hexane, 3:7, silica gel)

ORD record

ord-c2176d51f730456e9a67dafa4ffeba51

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06664274B1