Water → HCID 22495650, compound

HRID 1815836Notes

Reaction equation

HRID 1815836 reaction equation
Br[C:2]1[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=[C:4]([F:11])[CH:3]=1.[Mg].[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH:22]([CH3:27])[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>C(OCC)C.O1CCCC1.ClCCl>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([OH:26])([C:2]2[C:10]3[O:9][CH:8]=[CH:7][C:6]=3[CH:5]=[C:4]([F:11])[CH:3]=2)[CH:22]([CH3:27])[CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 962WaterHCID 5609651-Benzyl-3-methyl-4-piperidoneHCID 5462224MagnesiumHCID 221448167-Bromo-5-fluoro-1-benzofuran

Product 1

HCID 22495650HCID 22495650, compoundYield 77.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6.0 gm (27.9 mMol) 7-bromo-5-fluorobenzofuran and 0.70 gm (28.8 mMol) magnesium in 75 mL diethyl ether was heated at reflux for 30 minutes. To this mixture was then added a solution of 6.3 gm (31 mMol) 1-benzyl-3-methyl-4-oxopiperidine in 30 mL tetrahydrofuran dropwise over 15 minutes. The resulting mixture was heated at reflux for about 24 hours. The reaction mixture was cooled to room temperature and poured into 100 mL water. The resulting emulsion was diluted with 500 mL dichloromethane and then filtered through a bed of celite. The filter cake was washed with 2×200 mL dichloromethane. The filtrate aqueous phase was washed with 2×200 mL dichloromethane. All organic phases were combined, dried over magnesium sulfate, and concentrated under reduced pressure The residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0-50% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 7.3 gm (77%) of the desired compound.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for about 24 hours
  5. filtrationfiltered through a bed of celite
  6. washThe filter cake was washed with 2×200 mL dichloromethane
  7. washThe filtrate aqueous phase was washed with 2×200 mL dichloromethane
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure The residue
  10. washeluting with a gradient of hexane containing from 0-50% ethyl acetate
  11. additionFractions containing product
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d3456af462f54cf8beef386bbfaa5578
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

Loading…