反应详情

温度

85 °C

4-(difluoromethyl)pyrimidin-2-ol was diluted with phosphorus oxychloride (80 mL) then heated at 85° C. for 3 hours with periodic venting of the reaction mixture. The mixture was cooled to rt, diluted with DCM (500 mL) and poured into water (˜1 L) cooled in an ice bath at such a rate the exotherm was maintained at ˜30° C. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with DCM (2×500 mL) and the organics were combined and dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford 2-chloro-4-(difluoromethyl) as a light yellow oil. MS ESI calcd. for C5H4ClF2N2 [M+H]+ 165. found 165. 1H NMR δ ppm DMSO-d6): 8.18 (1H, d, J=6.25 Hz), 6.63 (1H, t, J=54.22 Hz). 6.57 (2H, d, J=6.26 Hz).

1. temperatureThe mixture was cooled to rt
2. temperaturecooled in an ice bath at such a rate the exotherm
3. temperaturewas maintained at ˜30° C
4. customThe mixture was transferred to a separatory funnel
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with DCM (2×500 mL)
7. dry with materialdried with anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto afford 2-chloro-4-(difluoromethyl) as a light yellow oil