反应详情

温度

80 °C

To a solution consisting of 5-(3-chloropropyl)-3-(2-fluorophenyl)-6,7-dihydro -1,2-benzisoxazol-4(5H)-one (6.4 g) and DMF (100 ml) was added anhydrous potassium carbonate (1.4 g), diisopropylethyl amine (5.4 ml), 1-(2-pyridyl)piperazine (4.8 ml) and potassium iodide (0.4 g) at room temperature with stirring. The flask was flushed with nitrogen and warmed to 80° C. for 16 hours. Upon cooling to room temperature, water and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with water twice, then brine and dried (MgSO4). Filtration and concentration gave the crude product. Purification via preparative HIPLC (silica gel, 3% methanol) afforded 4.2 g of 6,7-dihydro-3-(2-fluorophenyl)-5-[3-(4-(2-pyridyl)-1-piperazinyl)-propyl]-1,2-benzisoxazol-4(5H)-one, as an oil which solidified upon standing. The product was recrystallized from ether, m.p. 94°- 96° C.

1. customThe flask was flushed with nitrogen
2. temperatureUpon cooling to room temperature
3. additionwater and ethyl acetate were added to the reaction mixture
4. customThe layers were separated
5. extractionthe aqueous phase was extracted three times with ethyl acetate
6. washThe combined organic layers were washed with water twice
7. dry with materialbrine and dried (MgSO4)
8. filtrationFiltration and concentration
9. customgave the crude product
10. customPurification via preparative HIPLC (silica gel, 3% methanol)