Potassium Carbonate → 1-[3-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]-phenylmethanone

HRID 235368Notes

Reaction equation

HRID 235368 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:17]([O-:20])([O-])=O.[K+].[K+].Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:29]=[C:30]([C:36]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40]C=2)=O)[CH:31]=[CH:32][C:33]=1[O:34][CH3:35]>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:29]=[C:30]([C:36]5([CH:17]=[O:20])[CH:38]=[CH:43][CH:42]=[CH:41][CH2:40]5)[CH:31]=[CH:32][C:33]=4[O:34][CH3:35])[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 15378702[3-(3-Chloropropoxy)-4-methoxy-phenyl]phenyl-methanone

Product 1

HCID 867482501-[3-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]-phenylmethanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2 benzisoxazole (2.01 g; 9.13 mmol), K2CO3 (2.0 g), and ]-[3-(3-chloropropoxy)-4-methoxy-phenyl]phenyl-methanone (3.93 g; 11.3 mmol) and acetonitrile (50 ml) was heated at reflux for 4 hours. At the end of the reaction, the solvent was evaporated and the residue was partitioned between water (150 ml) and dichloromethane (400 ml). The dichioromethane solution was washed with water and brine (100 ml), dried over MgSO4, then concentrated to an oil. The purification was done by flash chromatography over a silica gel column (SiO2 40 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 850 ml). The material thus obtained as a colorless oil solidified on standing. Recrystallization from ethanol (150 ml) gave 1-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]-phenylmethanone as white crystals, 3.07 g (63%), m.p.=140°-141° C.

Workup

  1. temperatureat reflux for 4 hours
  2. customAt the end of the reaction
  3. customthe solvent was evaporated
  4. customthe residue was partitioned between water (150 ml) and dichloromethane (400 ml)
  5. washThe dichioromethane solution was washed with water and brine (100 ml)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated to an oil
  8. customThe purification
  9. washwas done by flash chromatography over a silica gel column (SiO2 40 g; eluted with dichloromethane, 300 ml; 1% methanol in dichloromethane, 850 ml)
  10. customThe material thus obtained as a colorless oil
  11. customRecrystallization from ethanol (150 ml)

Sources & evidence

ORD record
ord-2abdd7df2b7142bf85cbd29307c97d35
Source dataset
uspto-grants-1997_01
Patent number
US05597842

Reaction notes

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