反应详情

温度

-10 °C

n-BuLi (1.6M in hexane) (13.90 mL of 1.6 M, 22.24 mmol) was added to a solution of diisopropylamine (2.353 g, 3.259 mL, 23.25 mmol) in THF (50.00 mL) cooled to −5/−10° C. under N2. Fifteen minutes later, the solution was cooled to −78° C. A solution of tert-butyl-dimethyl-(2,3,5-trifluoro-4-pyridyl)silane (5 g, 20.22 mmol) in THF (10.00 mL) was added to the reaction mixture which was stirred for 45-50 min. 2-Fluoro-N-methoxy-N-methylnicotinamide (4.282 g, 23.25 mmol) was added to the reaction mixture which was stirred at −78° C. for a further 2 hours. The reaction mixture was quenched with a saturated ammonium chloride aqueous solution. It was diluted with ethyl acetate. The organic was washed with brine. It was dried over magnesium sulfate and concentrated in vacuo after filtration. The crude mixture was taken up in a 1M hydrazine solution in THF (80 mL of 1 M, 80.00 mmol) and stirred at room temperature for 18 hours. The brown solution was concentrated under reduced pressure. The residue was triturated with DCM. A brown solid was filtered off. The filtrate was partially concentrated and purified on silica gel eluting with petrol ether/ethyl acetate to afford the title compound as a beige solid (1.8 g, 30%). 1H NMR (CDCl3) 0.54 (6H, s), 1.03 (9H, s), 7.32-7.35 (1H, d), 8.70-8.71 (1H, d), 8.89-8.91 (1H, d), 12.1 (1H, s).

1. temperatureFifteen minutes later, the solution was cooled to −78° C
2. stirringwas stirred at −78° C. for a further 2 hours
3. customThe reaction mixture was quenched with a saturated ammonium chloride aqueous solution
4. additionIt was diluted with ethyl acetate
5. washThe organic was washed with brine
6. dry with materialIt was dried over magnesium sulfate
7. concentrationconcentrated in vacuo
8. filtrationafter filtration
9. stirringstirred at room temperature for 18 hours
10. concentrationThe brown solution was concentrated under reduced pressure
11. customThe residue was triturated with DCM
12. filtrationA brown solid was filtered off
13. concentrationThe filtrate was partially concentrated
14. custompurified on silica gel eluting with petrol ether/ethyl acetate