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

HRID 2184499Notes

Reaction equation

HRID 2184499 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 wax extracted into dichloromethane (150 ml). The insolubles were filtered off. -De 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°-10 3° C.

Workup

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

Sources & evidence

ORD record
ord-d873f0394da242ae966929056a60ba21
Source dataset
uspto-grants-2002_06
Patent number
USRE037729E1

Reaction notes

Loading…