反应详情

温度

65 °C

A reaction vial was charged with 5-bromopyrimidin-2-ol (1.50 g, 8.57 mmol), sodium 2-chloro-2,2-difluoroacetate (2.61 g, 17.14 mmol), potassium carbonate (2.1 equiv.) and DMF (10 mL). The resulting mixture was sparged with nitrogen for ˜5 min., then heated to 65° C. and stirred overnight (˜15 h). After cooling to rt, the resulting mixture was partitioned between EtOAc (300 mL) and water (100 mL). The layers were separated and the organic portion was washed with water (50 mL×2) then 80 mL of hexanes was added and washed again with water (50 mL×2), brine, then dried over sodium sulfate. The resulting solution was filtered and concentrated to remove solvent which afforded a colorless oil as the crude product mixture. This material was purified by ISCO silica gel chromatography (gradient Hex/EtOAc mixtures as eluant; 40 g column) Fractions containing the desired product were collected, combined and concentrated under vacuum to afford 186 mg (10%) of a colorless oil as the title compound. 1H NMR (400 MHz, METHANOL-d4) δ 8.95-8.71 (m, 2H), 7.83-7.27 (m, 1H).

1. customA reaction
2. customThe resulting mixture was sparged with nitrogen for ˜5 min.
3. temperatureAfter cooling to rt
4. customthe resulting mixture was partitioned between EtOAc (300 mL) and water (100 mL)
5. customThe layers were separated
6. washthe organic portion was washed with water (50 mL×2)
7. addition80 mL of hexanes was added
8. washwashed again with water (50 mL×2), brine
9. dry with materialdried over sodium sulfate
10. filtrationThe resulting solution was filtered
11. concentrationconcentrated
12. customto remove solvent which
13. customafforded a colorless oil as the crude product mixture
14. customThis material was purified by ISCO silica gel chromatography (gradient Hex/EtOAc mixtures as eluant; 40 g column) Fractions
15. additioncontaining the desired product
16. customwere collected
17. concentrationconcentrated under vacuum