反应详情

温度

-78 °C

To a solution of 3-butyn-1-yl tetrahydropyranyl ether (0.4815 g, 3.05 mmol) (prepared as in Example 1 above) in dry tetrahydrofuran (15 mL) at -78° C. is added n-butyllithium (3.05 mmol, 2.80 mL of 1.09M n-BuLi in hexane). The resulting yellow mixture is stirred for 1 hour at -78° C., warmed to -5° C. for about 5 min and then a solution of 8-bromo-1-fluorooctane (0.7716 g, 3.65 mmol, 1.2 eq.) in HMPA (10 mL) is added dropwise over 45 minutes (Hendry et al., J. Chem. Ecol., 1, 317, 1975). After the addition is completed, the reaction is allowed to warm to room temperature and stirred overnight. After quenching the solution by the dropwise addition of water (about 10 mL), the aqueous solution is extracted with pentane (4×50 ml) and the combined pentane extracts are washed with saturated sodium chloride (50 mL) and dried (MgSO4). The volatiles are removed in vacuo and the crude product is flash chromatographed using hexane/ethyl acetate (9:1, v/v) to give 12-fluoro-3-dodecyn-1-yl tetrahydropyranyl ether (0.526 g, 60%) as a clear colorless oil: Rf=0.60, hexane/ethyl acetate (7:3, v/v); IR (film) ν2850-3000 (alkane CH) and 1H-NMR (CDCl3) δ1.20-1.90 (m, 18H), 2.05-2.20 (m, 2H), 2.30-2.55 (m,2H), 3.30-3.95(m, 4, 4.42 (dt, J=48 Hz, 6 Hz, 2H), 4.60 (br s, 1H).

1. temperaturewarmed to -5° C. for about 5 min
2. additionAfter the addition
3. temperatureto warm to room temperature
4. stirringstirred overnight
5. customAfter quenching the solution
6. additionby the dropwise addition of water (about 10 mL)
7. extractionthe aqueous solution is extracted with pentane (4×50 ml)
8. washthe combined pentane extracts are washed with saturated sodium chloride (50 mL)
9. dry with materialdried (MgSO4)
10. customThe volatiles are removed in vacuo
11. customchromatographed