Potassium Carbonate → 1-[3-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl)ethanone fumarate

HRID 55577

Reaktionsgleichung

Reaktionsgleichung von HRID 55577
Cl.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[N:8][O:9][C:5]=2[CH:4]=1.[C:18]([O-:21])([O-:20])=O.[K+].[K+].Cl[CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:30]=[C:31]([C:35](=[O:37])[CH3:36])[CH:32]=[CH:33][CH:34]=1>C(#N)C>[C:5]([OH:28])(=[O:9])/[CH:6]=[CH:16]/[C:18]([OH:21])=[O:20].[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:25][CH2:26][CH2:27][O:28][C:29]4[CH:30]=[C:31]([C:35](=[O:37])[CH3:36])[CH:32]=[CH:33][CH:34]=4)[CH2:14][CH2:15]3)=[N:8][O:9][C:5]=2[CH:4]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 11334359R-56109 hydrochlorideHCID 143487521-[3-(3-Chloropropoxy)phenyl]ethanone

Produkt 1

HCID 219600981-[3-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl)ethanone fumarateAusbeute 48,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 5 hours
  3. customAt the end of the reaction
  4. customthe solvent was removed
  5. extractionthe residue was extracted into dichloromethane (300 ml)
  6. filtrationThe inorganic insolubles were filtered off
  7. concentrationThe dichloromethane solution was concentrated to a small volume (10 ml)
  8. custompurified on a flash chromatographic column (SiO2, 75 g, eluted with dichloromethane, 900 ml; and 2% methanol in dichloromethane, 800 ml)
  9. additionThe fractions containing the pure product
  10. concentrationconcentrated to an oil (2.87 g, 35%)
  11. dissolutionThe oil was dissolved into ethanol
  12. additiontreated with a solution of fumaric acid (841 mg)
  13. customRecrystallization (twice) from ethanol

Quellen und Nachweise

ORD-Eintrag
ord-e792178b99404dd4aa889a254589a127
Quelldatensatz
uspto-grants-1997_04
Patentnummer
US05624927

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