Potassium Carbonate → 1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methylsulfanyl-phenyl)-ethanone

HRID 1899474Notes

Reaction equation

HRID 1899474 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[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=1[S:37][CH3:38]>C(#N)C>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:24][CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=4[S:37][CH3:38])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 100406381-[4-(3-Bromopropoxy)-3-methylmercaptophenyl]ethanone

Product 1

HCID 103211391-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methylsulfanyl-phenyl)-ethanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (1.88 g, 8.5 mmol), K2CO3 (1.8 g) and 1-[4-(3-bromopropoxy)-3-methylmercaptophenyl]ethanone (2.3 g, 7.6 mmol) in acetonitrile (100 ml) was heated at reflux for 4 hours. At the end of the reaction, the solvent was concentrated, then diluted with dichloromethane (250 ml). The insolubles were filtered off. The dichloromethane solution was concentrated to dryness as an oil. Purification was effected by flash chromatography on a silica gel column (SiO2, 54 g, eluted with dichloromethane, 500 ml; 1% methanol-dichloromethane, 1.1 l). The purest fractions were combined to give a colorless oil which solidified to an off-white solid (2.4 g). Recrystallization from ethanol (100 ml) yielded 1-[4-[3-[4-(6-fluoro-1,2-benzoisoxazol-3-yl]-1-piperidinyl]propoxy]-3-methylmercaptophenyl]ethanone as off-white needle crystals, 2.15 g, m.p.=150°-152° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. customAt the end of the reaction
  4. concentrationthe solvent was concentrated
  5. additiondiluted with dichloromethane (250 ml)
  6. filtrationThe insolubles were filtered off
  7. concentrationThe dichloromethane solution was concentrated to dryness as an oil
  8. customPurification
  9. washwas effected by flash chromatography on a silica gel column (SiO2, 54 g, eluted with dichloromethane, 500 ml; 1% methanol-dichloromethane, 1.1 l)
  10. customto give a colorless oil which
  11. customRecrystallization from ethanol (100 ml)

Sources & evidence

ORD record
ord-229da0cfe78b4192b046b011a1289801
Source dataset
uspto-grants-1996_11
Patent number
US05571828

Reaction notes

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