3-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole → 1-[3-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]-phenylmethanone

HRID 233828Notes

Reaction equation

HRID 233828 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.Cl[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:23]=[C:24]([C:30]2([CH:36]=[O:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH2:31]2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]>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]([CH2:18][CH2:19][CH2:20][O:21][C:22]4[CH:23]=[C:24]([C:30]5([CH:36]=[O:37])[CH:31]=[CH:32][CH:33]=[CH:34][CH2:35]5)[CH:25]=[CH:26][C:27]=4[O:28][CH3:29])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 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), K2CO2 (2.0 g), and 1-[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 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.

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-e6bd9ca8d7c241f083d71f0beaf3d8dd
Source dataset
uspto-grants-1997_01
Patent number
US05593995

Reaction notes

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