反应详情

温度

-70 °C

TMEDA (2.54 ml, 16.8 mmol) is added to a solution of pivaloylamino pyridine (1 g, 5.6 mmol) in diethyl ether (40 ml), and the resulting solution is cooled to −70° C. A solution of 2.5M N-Butyl lithium in hexanes (6.73 ml, 16.8 mmol) is added dropwise to the solution, which turns a golden yellow colour. The solution is allowed to warm to −20° C. and stirred at this temperature for 2 hours. The solution is cooled to −70° C. and a solution of pyridine-3-carbaldehyde (1.16 ml, 12.3 mmol) in THF (20 ml) is added and resulting suspension is allowed to warm to room temperature and stirred overnight. H2O is added and the phases are separated, the aqueous phase is washed with DCM, and the organic phases combined, and concentrated in vacuo to afford a yellow oil. Purification by flash chromatography (SiO2, 70-100% EtOAc in iso-hexane), and drying in vacuo at 45° C. overnight yields N-[3-(hydroxyl-pyridin-2-yl-methyl)-pyridin-2-yl]-2,2-dimethyl-propionamide [M+H]+ 286.

1. temperatureto warm to −20° C.
2. temperatureThe solution is cooled to −70° C.
3. customresulting suspension
4. temperatureto warm to room temperature
5. stirringstirred overnight
6. customthe phases are separated
7. washthe aqueous phase is washed with DCM
8. concentrationconcentrated in vacuo
9. customto afford a yellow oil
10. customPurification by flash chromatography (SiO2, 70-100% EtOAc in iso-hexane)
11. customdrying in vacuo at 45° C. overnight