1-Benzyl-4-piperidone → HCID 18797502, compound

HRID 1003584Notes

Reaction equation

HRID 1003584 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH2:27]([N:34]1[CH2:39][CH2:38][C:37](=[O:40])[CH2:36][CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCCC1>[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[C:19]2[C:37]2([OH:40])[CH2:38][CH2:39][N:34]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:35][CH2:36]2)(=[O:17])=[O:16])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 192201-Benzyl-4-piperidoneHCID 3150171-(Phenylsulfonyl)-1H-indoleHCID 2724682Lithium diisopropylamide

Product 1

HCID 18797502HCID 18797502, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of lithium diisopropylamide (15.5 mMol in tetrahydrofuran) was added via cannula to a solution of 4.0 gm (15.5 mMol) 1-phenylsulfonyl-1H-indole in 100 mL tetrahydrofuran at -78° C. The reaction mixture was stirred at this temperature for 1.5 hours, warmed to room temperature for 1 hour and then cooled again to -78° C. To this solution was then added a solution of 2.94 mL (15.9 mMol) 1-benzyl-4-piperidinone in tetrahydrofuran and the resulting mixture was allowed to warm to room temperature over 18 hours. The reaction mixture was then partitioned between saturated aqueous sodium bicarbonate and diethyl ether. The phases were separated and the organic phase washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a dichloromethane gradient containing 0-2% methanol. Fractions shown to contain product were combined and concentrated under reduced pressure to provide 3.23 gm (47%) of the desired compound as an off-white solid.

Workup

  1. temperaturecooled again to -78° C
  2. temperatureto warm to room temperature over 18 hours
  3. customThe reaction mixture was then partitioned between saturated aqueous sodium bicarbonate and diethyl ether
  4. customThe phases were separated
  5. washthe organic phase washed with saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluting with a dichloromethane gradient
  9. additioncontaining 0-2% methanol
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-979f66211e604f0d9afb3fb2622b9e66
Source dataset
uspto-grants-2000_04
Patent number
US06046215

Reaction notes

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