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

HRID 976667Notes

Reaction equation

HRID 976667 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 dichioromethane (400 ml). The dichloromethane solution was washed with water and brine (1(30 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-benzisoxa zol-3-yl)-1-piperidinyl]propoxy]-4-me as white crystals, 3.07 g (63%), m.p. =140°-141° C.

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 dichioromethane (400 ml)
  6. washThe dichloromethane solution was washed with water and brine (1(30 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)
  13. customgave 1-[3-[3-[4-(6-fluoro-1,2-benzisoxa zol-3-yl)-1-piperidinyl]propoxy]-4-me as white crystals, 3.07 g (63%)
  14. custom=140°-141° C.

Sources & evidence

ORD record
ord-bb945c8ddf684b0caeeb5542cb347fc5
Source dataset
uspto-grants-1997_03
Patent number
US05612342

Reaction notes

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