Phosphorus oxybromide → 2-Bromo-5-chloro-3-fluoropyridine

Participants

Reaction Conditions

Reaction Steps

To solid 5-chloro-3-fluoro-2-hydroxypyridine (75 g, 0.51 mmol) was added melted POBr3 (150 g, 0.52 mmol). DMF (2 mL) was then added by pipet, and the mixture was heated at 130° C. for 1 h. The excess POBr3 was quenched by the careful addition of water to the reaction mixture at 0° C., and the resulting mixture was dissolved in a 2:1 mixture of EtOAc:water. The organic layer was washed three times with water and once with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting yellow oil was passed through a plug of silica gel (10% Et2O:90% hexanes) to provide the title compound as a white solid (79.4 g, 74%). The product was characterized by 1H NMR.

Provenance & Evidence