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

HRID 370149Notes

Reaction equation

HRID 370149 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]2([CH:40]=[O:41])[CH:39]=[CH:38][CH:37]=[CH:36][CH2:35]2)=[CH:30][C:29]=1[O:42][CH3:43]>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]5([CH:40]=[O:41])[CH:35]=[CH:36][CH:37]=[CH:38][CH2:39]5)=[CH:30][C:29]=4[O:42][CH3:43])[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 867482531-[4-(3-Bromopropoxy)-3-methoxyphenyl] phenylmethanone

Product 1

HCID 867482521-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-piperidinyl]propoxy]-3-methoxyphenyl]-phenylmethanoneYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10 mmol), K2CO3 (2.3 g) and 1-[4-(3-bromopropoxy)-3-methoxyphenyl]phenylmethanone (3.47 g, 10 mmol) in acetonitrile (100 ml) was heated at reflux for 3 hours. At the end of reaction, the acetonitrile was concentrated and the mixture was extracted into dichloromethane (200 ml). The insolubles were filtered off and the solvent was evaporated to an oil. Purification was carried out by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 600 ml; 1% methanol:dichloromethane, 600 ml; 2% methanol: 98% dichloromethane, 600 ml). The fractions containing the pure product were combined and concentrated to give 4.24 g (87%) of an off-white solid. Recrystallization from ethanol (75 ml) gave 3.9 g of 1-[4-[3-[4-(6-fluoro-1,2-benziosoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]phenylmethanone as off-white crystals, m.p.=128-130° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. customAt the end of reaction
  4. concentrationthe acetonitrile was concentrated
  5. extractionthe mixture was extracted into dichloromethane (200 ml)
  6. filtrationThe insolubles were filtered off
  7. customthe solvent was evaporated to an oil
  8. customPurification
  9. washwas carried out by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 600 ml; 1% methanol:dichloromethane, 600 ml; 2% methanol: 98% dichloromethane, 600 ml)
  10. additionThe fractions containing the pure product
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-f508f8e082824c38a44d65e3f810e7db
Source dataset
uspto-grants-2000_10
Patent number
US06140345

Reaction notes

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