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

HRID 233830

반응식

HRID 233830 반응식
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

참가 물질

5

반응물 3

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

생성물 1

HCID 219600981-[3-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl)ethanone fumarate수율 48.2%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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

후처리

  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

출처 및 근거

ORD 기록
ord-cc4955fb4be1460ebb058ea4328a554c
출처 데이터셋
uspto-grants-1997_01
특허 번호
US05593995

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