反应详情

温度

4 °C

Triflic anhydride (13.9 g, 85 mmol) in dry DCM (70 mL) was added slowly to an ice-cold solution of 2-(trifluoromethyl)pyrimidin-5-ol (13.9, 85 mmol) (U.S. Pat. No. 4,558,039), DIPEA (16 mL, 93 mmol) and dry DCM (260 mL) at such a rate that the temperature was kept between 4° C. and 6° C. After the addition was complete, the solution was stirred for 2.5 h at 4° C. and then allowed to warm to RT. Water (50 mL) and 1M phosphoric acid (4.5 mL) were added and the phases were washed and separated. The organic phase was washed successively with water and saturated sodium bicarbonate, dried, filtered and carefully concentrated by rotary evaporation (pressure 300-400 mbar). The dark-red oil was purified by column chromatography with EtOAc-heptanes (1:8 through 1:4) as eluent to give 22.5 g (90%) of the title product as a colourless oil that crystallised in the cold. Alternatively, the product could be purified by distillation, b.p. 75-77° C./10 mbar.

1. customwas kept between 4° C. and 6° C
2. additionAfter the addition
3. temperatureto warm to RT
4. washthe phases were washed
5. customseparated
6. washThe organic phase was washed successively with water and saturated sodium bicarbonate
7. customdried
8. filtrationfiltered
9. concentrationcarefully concentrated by rotary evaporation (pressure 300-400 mbar)
10. customThe dark-red oil was purified by column chromatography with EtOAc-heptanes (1:8 through 1:4) as eluent