反应详情

温度

-78 °C

A mixture of lithium diisopropylamide (2 M in heptane/THF/ethylbenzene, stabilised with 0.5% w/w LiBr; 3.8 ml, 7.6 mmol) and THF (3 ml) was cooled to −78° C. and a solution of 2-chloro-3-fluoropyridine (1.0 g, 7.6 mmol) in THF (2 ml) was added dropwise over 1 min. After 2 h, a solution of hexachloroethane (2.0 g, 8.4 mmol) in THF (3 ml) was added dropwise and stirring continued for 2 h before quenching with saturated aqueous NH4Cl solution (20 ml) and extraction of the reaction product with EtOAc (100 ml). The organic phase was dried over anhydrous MgSO4 and concentrated in vacuo. The crude material was purified by column chromatography (silica; 15% Et2O/isohexane) to afford 2,4-dichloro-3-fluoropyridine (795 mg, 63%): δH (400 MHz, CDCl3) 7.34 (1H, t, J 5.1), 8.13 (1H, d, J 5.1); m/z (ES+) 166 (100%, [MH]+).

1. waitcontinued for 2 h
2. custombefore quenching with saturated aqueous NH4Cl solution (20 ml) and extraction of the reaction product with EtOAc (100 ml)
3. dry with materialThe organic phase was dried over anhydrous MgSO4
4. concentrationconcentrated in vacuo
5. customThe crude material was purified by column chromatography (silica; 15% Et2O/isohexane)