反応 #2298659

反応方程式

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

収率 48.2%

溶媒

acetonitrile

反応条件

後処理

1. 1
   温度was heated
2. 2
   温度at reflux for 5 hr
3. 3
   その他At the end of the reaction
4. 4
   その他the solvent was removed
5. 5
   抽出the residue was extracted into dichloromethane (300 ml)
6. 6
   ろ過The inorganic insolubles were filtered off
7. 7
   濃縮The dichloromethane solution was concentrated to a small volume (10 ml)
8. 8
   その他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
    濃縮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
    その他Recrystallization (twice) from ethanol

実験手順

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (4.53 gm, 20.5 mmoles), K2CO3 (4.5 gm), 1-[3-(3-chloropropoxy)phenyl]ethanone (6.4 g, 29 mmoles) in acetonitrile (60 ml) was heated at reflux for 5 hr. 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.

出典