반응 #320324

반응 방정식

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

K2CO3

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

→

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

수율 48.2%

용매

acetonitrile

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도at reflux for 5 hours
3. 3
   기타At the end of the reaction
4. 4
   기타the solvent was removed
5. 5
   추출the residue was extracted into dichloromethane (300 ml)
6. 6
   여과The inorganic insolubles were filtered off
7. 7
   농축The dichloromethane solution was concentrated to a small volume (10 ml)
8. 8
   기타purified 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
    농축concentrated 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
    기타Recrystallization (twice) from ethanol

실험 절차

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-l,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone fumarate as white crystals, m.p.=172°-174° C.

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