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

HRID 1082617Notes

Reaction equation

HRID 1082617 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+].Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:29]=[C:30]([C:36]2([CH:42]=[O:43])[CH:41]=[CH:40][CH:39]=[CH:38][CH2:37]2)[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:42]=[O:43])[CH:37]=[CH:38][CH:39]=[CH:40][CH2:41]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 867482511-[3-(3-Chloropropoxy)-4-methoxyphenyl]phenylmethanone

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 1-[3-(3-chloropropoxy)-4-methoxy-phenyl]phenylmethanone (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 dichloromethane 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. ANALYSIS: Calculated for C29H29FN2O4 : 71.30%C 5.98%H 5.73%N Found: 71.09%C 5.98%H 5.73%N

Workup

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

Sources & evidence

ORD record
ord-62e1b85fa6c7419e8e590f2b62b6d934
Source dataset
uspto-grants-1996_12
Patent number
US05589495

Reaction notes

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