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

Temperature

130 °C

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.

1. customThe excess POBr3 was quenched by the careful addition of water to the reaction mixture at 0° C.
2. dissolutionthe resulting mixture was dissolved in a 2:1 mixture of EtOAc
3. washThe organic layer was washed three times with water
4. dry with materialonce with brine, dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-ec0beacc0f464820b88661767beabebb

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989469B2