反应详情

温度

80 °C

A solution of ethylene carbonate (121 g, 1376.13 mmol) in DMF (200 mL) was added dropwise to a stirred suspension of 4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol (100 g, 275.23 mmol) and potassium carbonate (76 g, 550.45 mmol) in DMF (200 mL) at 80° C. over a period of 15 minutes under nitrogen. The resulting mixture was stirred at 80° C. for 20 hours. The reaction mixture was cooled to room temperature, then concentrated and diluted with DCM (2 L), and washed sequentially with water (1 L) and saturated brine (500 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 70 to 100% EtOAc in isohexane. Fractions containing the desired product were evaporated to dryness then triturated with EtOAc (150 mL). The resulting solid was washed with further EtOAc (50 mL) and ether then dried to give 2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethanol. The filtrate was evaporated and further purified by flash silica chromatography, elution gradient 70 to 100% EtOAc in isohexane. Fractions containing the desired product were evaporated to dryness then triturated with ether, dried and combined with the material previously collected to afford 2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethanol (89 g, 79%) as a solid.

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationconcentrated
3. additiondiluted with DCM (2 L)
4. washwashed sequentially with water (1 L) and saturated brine (500 mL)
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. customevaporated
8. customto afford crude product
9. customThe crude product was purified by flash silica chromatography, elution gradient 70 to 100% EtOAc in isohexane
10. additionFractions containing the desired product
11. customwere evaporated to dryness
12. customthen triturated with EtOAc (150 mL)
13. washThe resulting solid was washed with further EtOAc (50 mL) and ether
14. customthen dried