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

Temperature

120 °C

5-Bromo-2-methylpyrimidin-4-ol (MM1) (30 g, 159 mmol) was suspended in phosphorous oxychloride (150 mL). The reaction mixture was heated at 120° C. for 30 minutes. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and azeotroped twice with toluene. The crude residue was diluted with EtOAc (600 mL) and cooled to 0° C. Aqueous sodium bicarbonate (150 mL) was slowly added with stirring. The organic layer was washed once more with sodium bicarbonate (150 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. LRMS m/z (M+H) 207.0 found, 207.4 required.

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 (600 mL)
5. temperaturecooled to 0° C
6. additionAqueous sodium bicarbonate (150 mL) was slowly added
7. washThe organic layer was washed once more with sodium bicarbonate (150 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-cdcfede0e8cb46b1b59153fc12604909

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975261B2