Phosphorus oxychloride → 5-Bromo-4-chloro-2-methylpyrimidine

Temperature

120 °C

5-Bromo-2-methylpyrimidin-4-ol (5 g, 2.6 mmol) was suspended in phosphorous oxychloride (100 mL). The reaction mixture was heated at 120° C. for 60 minutes. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and azeotroped twice with toluene. The crude residue was diluted with EtOAc (100 mL) and cooled to 0° C. Aqueous sodium bicarbonate (20 mL) was slowly added with stirring. The organic layer was washed once more with sodium bicarbonate (20 mL), dried over MgSO4, filtered and concentrated in vacuo to afford the title compound as a dark oil, which was sufficiently pure to use in the subsequent step without further purification (5.3 g, 98%): LC/MS m/z=207.0 (M+H)+.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. concentrationconcentrated in vacuo
3. customazeotroped twice with toluene
4. additionThe crude residue was diluted with EtOAc (100 mL)
5. temperaturecooled to 0° C
6. additionAqueous sodium bicarbonate (20 mL) was slowly added
7. washThe organic layer was washed once more with sodium bicarbonate (20 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-17fcef0f60d94f668afaee106ff7e1b4

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273033B2