Trimethylsilylacetylene → 7-ethynyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ol

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence