反应详情

温度

80 °C

A solution of ethylene carbonate (18.18 g, 206.42 mmol) in DMF (30 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 (obtained as described in Example 4.2, preparation of starting materials) (15 g, 41.28 mmol) and potassium carbonate (11.41 g, 82.57 mmol) in DMF (30 mL) at 80° C. over a period of 10 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 (500 mL), and washed sequentially with water (500 mL) and saturated brine (250 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. Pure fractions were evaporated to dryness to give 2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethanol (12.04 g, 71.6%) as a solid.

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationthen concentrated
3. additiondiluted with DCM (500 mL)
4. washwashed sequentially with water (500 mL) and saturated brine (250 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. customPure fractions were evaporated to dryness