反应详情

温度

-78 °C

To a solution of n-butyllithium (2.5M in hexane, 19.5 ml, 48.75 mmol) in THF (15 ml) at −78° C. was added dropwise ethynyl(trimethyl)silane (6.41 ml, 45.06 mmol). The reaction was stirred at −78° C. for 20 minutes and then a solution of 5,6-dihydro-7H-cyclopenta[b]pyridin-7-one (5 g, 7.51 mmol) in THF (25 mL) was added. The reaction mixture was stirred at −78° C. to RT for 4 hr. The mixture was then diluted with water and the volatiles removed in vacuo. The product was extracted with CHCl3:IPA (2:1 ratio, 3×30 ml) and the organic phase was washed with water (30 mL), brine (30 mL); dried over Na2SO4, filtered and concentrated in vacuo. Purification by column chromatography (Biotage), eluting with 0-5% MeOH-DCM followed by another column chromatography purification with 30% EtOAc/heptanes gave the title compound; 1H NMR (500 MHz, CDCl3) 2.49 (1H, ddd, J=13.44, 8.24, 6.07 Hz), 2.63-2.76 (2H, m), 2.90-3.02 (1H, m), 3.03-3.13 (1H, m), 3.42 (1H, s), 7.22 (1H, dd, J=7.57, 4.89 Hz), 7.62 (1H, d, J=7.57 Hz), 8.51 (1H, d, J=4.73 Hz); LC-MS: m/z=+159.9 (M+H)+.

1. stirringThe reaction mixture was stirred at −78° C. to RT for 4 hr
2. customthe volatiles removed in vacuo
3. extractionThe product was extracted with CHCl3:IPA (2:1 ratio, 3×30 ml)
4. washthe organic phase was washed with water (30 mL), brine (30 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification by column chromatography (Biotage)
9. washeluting with 0-5% MeOH-DCM
10. customfollowed by another column chromatography purification with 30% EtOAc/heptanes