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

HRID 1449878Notes

Reaction equation

HRID 1449878 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. ANALYSIS: Calculated for C29H29FN2O4 : 71.30%C 5.98%H 5.73%N Found: 71.31 %C 5.99%H 5.75%N

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-b4f8338fdbfc4b6184c99f181834d760
Source dataset
uspto-grants-1997_02
Patent number
US05599821

Reaction notes

Loading…