反应 #321012

反应方程式

6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride

K2CO3

1-[3-(3-chloropropoxy)phenyl]ethanone

→

1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone fumarate

收率 48.2%

溶剂

acetonitrile

反应条件

后处理

1. 1
   温度was heated
2. 2
   温度at reflux for 5 hours
3. 3
   其他At the end of the reaction
4. 4
   其他the solvent was removed
5. 5
   萃取the residue was extracted into dichloromethane (300 ml)
6. 6
   过滤The inorganic insolubles were filtered off
7. 7
   浓缩The dichloromethane solution was concentrated to a small volume (10 ml)
8. 8
   其他purified on a flash chromatographic column (SiO2, 75 g, eluted with dichloromethane, 900 ml; and 2% methanol in dichloromethane, 800 ml)
9. 9
   workup.ADDITIONThe fractions containing the pure product
10. 10
    浓缩concentrated to an oil (2.87 g, 35%)
11. 11
    workup.DISSOLUTIONThe oil was dissolved into ethanol
12. 12
    workup.ADDITIONtreated with a solution of fumaric acid (841 mg)
13. 13
    其他Recrystallization (twice) from ethanol

实验过程

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (4.53 g, 20.5 mmol), K2CO3 (4.5 g), 1-[3-(3-chloropropoxy)phenyl]ethanone (6.4 g 29 mmol) in acetonitrile (60 ml) was heated at reflux for 5 hours. At the end of the reaction, the solvent was removed and the residue was extracted into dichloromethane (300 ml). The inorganic insolubles were filtered off. The dichloromethane solution was concentrated to a small volume (10 ml) and purified on a flash chromatographic column (SiO2, 75 g, eluted with dichloromethane, 900 ml; and 2% methanol in dichloromethane, 800 ml). The fractions containing the pure product were combined and concentrated to an oil (2.87 g, 35%). The oil was dissolved into ethanol and treated with a solution of fumaric acid (841 mg). Recrystallization (twice) from ethanol afforded 2.53 g of 1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone fumarate as white crystals, m.p.=172°-174° C.

来源