反应详情

温度

-78 °C

To a solution of LDA (6.22 mmol, prepared from diisopropylamine (0.81 mL) and n-BuLi (2.5M in hexanes, 2.49 mL) in THF (5.0 mL) at 0° C. was added N-(propylidene)-cyclohexylamine (0.89 mL, 6.47 mmol, prepared in situ from propionaldehyde and cyclohexylamine) dropwise, and the reaction mixture was stirred for 20 minutes. To this solution at 0° C. was added DMPU (6.22 mmol), the mixture was stirred for 10 minutes, then cooled to -78° C. To this solution was added 4-t-butoxy-5-fluoro-3-methylpyridine (0.50 mL, 2.49 mmol) dropwise, and the mixture was warmed to -20° C. and stirred at this temperature for 16 hours. The reaction was then quenched with acetic acid (1M, 15 mL), diluted with hexanes (100 mL) and dilute acetic acid (1M, 85 mL), and stirred vigorously for 1 hour. The organic layer was separated, washed with water, dried (MgSO4) and concentrated. The residue was purified by chromatography on silica gel, eluting with 5% to 10% ethyl acetate in hexanes, to afford the title compound (0.24 g, 49% yield) as an oil. MS 240 (M+H)+ ; 1H NMR (CDCl3) δ1.43 (d, 3H, J=7.0 Hz), 1.43 (d, 9H, J=1.1 Hz), 2.26 (s, 3H), 3.84 (q, 1H, J =7.0 Hz), 8.26 (d, 1H, J=2.2 Hz), 9.78 (d, 1H, J=1.1 Hz).

1. stirringthe mixture was stirred for 10 minutes
2. temperaturethe mixture was warmed to -20° C.
3. stirringstirred at this temperature for 16 hours
4. customThe reaction was then quenched with acetic acid (1M, 15 mL)
5. additiondiluted with hexanes (100 mL) and dilute acetic acid (1M, 85 mL)
6. stirringstirred vigorously for 1 hour
7. customThe organic layer was separated
8. washwashed with water
9. dry with materialdried (MgSO4)
10. concentrationconcentrated
11. customThe residue was purified by chromatography on silica gel
12. washeluting with 5% to 10% ethyl acetate in hexanes