Hexachloroethane → 2,4-Dichloro-3-fluoropyridine

Temperature

-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)

ORD record

ord-60328b63c1204a25aa1b8f6c3d51f28c

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279580B2