1-Benzyl-4-piperidone → HCID 53979967, compound

HRID 1416196Notes

Reaction equation

HRID 1416196 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:12])[CH:8]=2)[CH:3]=1.[H-].[K+].C([Li])(C)(C)C.[CH2:20]([N:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1>[CH2:20]([N:27]1[CH2:32][CH2:31][C:30]([OH:33])([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([OH:12])[CH:8]=3)[CH:3]=2)[CH2:29][CH2:28]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 192201-Benzyl-4-piperidoneHCID 271446-Bromo-2-naphthalenolHCID 82127Potassium hydrideHCID 178418306HCID 178418306, compound

Product 1

HCID 53979967HCID 53979967, compoundYield 15.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 10.0 gm (44.8 mMol) 2-bromo-6-hydroxynaphthalene in tetrahydrofuran was added dropwise to a suspension of 9.42 gm (47.1 mMol) potassium hydride (20% suspension) in 180 mL tetrahydrofuran at 0° C. After stirring at this temperature for 2 hours the reaction mixture was cooled further to -78° C. and to it was added dropwise 58 mL (98.6 mMol) tert-butyllithium (1.7M in tetrahydrofuran). The mixture was stirred for 20 minutes at this temperature and then a solution of 8.73 mL (47.1 mMol) 1-benzyl-4-piperidone in 30 mL tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm gradually to room temperature and was stirred at this temperature for 18 hours. The reaction mixture was then partitioned between ethyl acetate and dilute ammonium hydroxide. The phases were separated and the aqueous phase was extracted well with ethyl acetate. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with 5% methanol in dichloromethane. Fractions containing product were combined and concentrated under reduced pressure to provide 2.27 gm (15%) of the desired product.

Workup

  1. stirringThe mixture was stirred for 20 minutes at this temperature
  2. temperatureto warm gradually to room temperature
  3. stirringwas stirred at this temperature for 18 hours
  4. customThe reaction mixture was then partitioned between ethyl acetate and dilute ammonium hydroxide
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted well with ethyl acetate
  7. washwashed with saturated aqueous sodium chloride
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. washeluting with 5% methanol in dichloromethane
  11. additionFractions containing product
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-18a5a3d0dc344d38bea19fd4b2892dda
Source dataset
uspto-grants-1999_06
Patent number
US05912256

Reaction notes

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