反应详情

温度

-78 °C

To a solution of n-butyllithium (2.5M in hexane, 2.1 ml, 5.32 mmol) in THF (3 mL) at −78° C. was added dropwise ethynyl(trimethyl)silane (0.7 mL, 4.91 mmol). The reaction was stirred at −78° C. for 10 minutes and then 1-(pyrimidin-4-yl)ethanone (0.5 g, 4.09 mmol) was added in more THF (2 mL). The reaction was stirred at −78° C. to RT overnight. The mixture was diluted with water and the volatiles removed in vacuo. The product was then extracted with CHCl3:IPA (2:1 ratio, 2×25 mL). The organic phase was washed with water (20 mL), brine (20 mL); dried over Na2SO4 and the solvent removed in vacuo. Purification by column chromatography (Biotage), eluting with 0-100% EtOAc-heptane afforded 2-(pyrimidin-4-yl)-4-(trimethylsilyl)but-3-yn-2-ol; 1H NMR (500 MHz, CDCl3) delta 0.19 (9H, s), 1.78 (3H, s), 4.65 (1H, s), 7.65 (1H, dd, J=5.20, 1.10 Hz), 8.79 (1H, d, J=5.36 Hz), 9.20 (1H, s); LC-MS: m/z=+221 (M+H)+; and 2-(pyrimidin-4-yl)but-3-yn-2-ol; 1H NMR (500 MHz, CDCl3) delta 1.79 (3H, s), 2.62 (1H, s), 4.99 (1H, s), 7.67 (1H, dd, J=5.28, 0.87 Hz), 8.77 (1H, d, J=5.36 Hz), 9.19 (1H, s); LC-MS: m/z=+148.95 (M+H)+.

1. stirringThe reaction was stirred at −78° C. to RT overnight
2. customthe volatiles removed in vacuo
3. extractionThe product was then extracted with CHCl3:IPA (2:1 ratio, 2×25 mL)
4. washThe organic phase was washed with water (20 mL), brine (20 mL)
5. dry with materialdried over Na2SO4
6. customthe solvent removed in vacuo
7. customPurification by column chromatography (Biotage)
8. washeluting with 0-100% EtOAc-heptane