Potassium Carbonate → 1-[3,5-Dibromo-4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone

HRID 866104Notes

Reaction equation

HRID 866104 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][CH2:25][CH2:26][O:27][C:28]1[C:33]([Br:34])=[CH:32][C:31]([C:35](=[O:37])[CH3:36])=[CH:30][C:29]=1[Br:38]>C(#N)C>[Br:34][C:33]1[CH:32]=[C:31]([C:35](=[O:37])[CH3:36])[CH:30]=[C:29]([Br:38])[C:28]=1[O:27][CH2:26][CH2:25][CH2:24][N:12]1[CH2:11][CH2:10][CH:9]([C:6]2[C:5]3[CH:15]=[CH:16][C:2]([F:1])=[CH:3][C:4]=3[O:8][N:7]=2)[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 219601181-[4-(3-Bromopropoxy)-3,5-dibromophenyl]ethanone

Product 1

HCID 219600591-[3,5-Dibromo-4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanoneYield 58.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2- benzisoxazole (2.0 g, 9.0 mmol), K2CO3 (1.3 g), and 1-[4-(3-bromopropoxy)-3,5-dibromophenyl]ethanone (2.65 g, 9.0 mmol) and acetonitrile (50 ml) was heated at reflux for 3 hours. At the end of the reaction, the solvent was evaporated and the residue was extracted into dichloromethane (150 ml). The insolubles were filtered off. The dichloromethane solution was concentrated down to an oil. The purification was done by flash chromatography on a silica gel column (SiO2, 47 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 600 ml). The material thus purified as a colorless oil, solidified on standing. Recrystallization from ethanol gave 1-[3,5-dibromo-4-[3-[4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]ethanone as white crystals (2.93 g, 57%), m.p.=102°-103° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. customAt the end of the reaction
  4. customthe solvent was evaporated
  5. extractionthe residue was extracted into dichloromethane (150 ml)
  6. filtrationThe insolubles were filtered off
  7. concentrationThe dichloromethane solution was concentrated down to an oil
  8. customThe purification
  9. washwas done by flash chromatography on a silica gel column (SiO2, 47 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 600 ml)
  10. customThe material thus purified as a colorless oil
  11. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-599f245616d941088990b5e958196b2c
Source dataset
uspto-grants-1996_10
Patent number
US05569653

Reaction notes

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