Methyl iodide → 1-Benzyl-3-methyl-4-piperidone

HRID 362542Notes

Reaction equation

HRID 362542 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[CH2:9]([N:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CI>C1COCC1>[CH2:9]([N:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH:18]([CH3:2])[CH2:17]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 192201-Benzyl-4-piperidoneHCID 2724682Lithium diisopropylamide

Product 1

HCID 5609651-Benzyl-3-methyl-4-piperidoneYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a -78° C. solution of LDA (10.79 mmol) in THF (30 mL) was added 1-benzyl-4-piperidone (2.0 mL, 10.8 mmol). The reaction mixture was warmed to 0° C. for 20 min and then cooled back to -78° C. Methyl iodide (0.67 mL, 10.8 mmol) was added to the enolate solution which was stirred at 0° C. for 2 h then warmed to RT overnight. The reaction mixture was quenched with sat. NH4Cl and concentrated. The residue was suspended in H2O and extracted with CH2Cl2. The combined organic layers were dried with MgSO4, filtered and concentrated. The product was purified by flash chromatography on silica gel eluting with 1:1 hexane-EtOAc to give the 1-benzyl-3-methyl-4-piperidone 4 as a yellow oil (0.65 g, 30%).

Workup

  1. temperaturecooled back to -78° C
  2. temperaturethen warmed to RT overnight
  3. customThe reaction mixture was quenched with sat. NH4Cl
  4. concentrationconcentrated
  5. extractionextracted with CH2Cl2
  6. dry with materialThe combined organic layers were dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was purified by flash chromatography on silica gel eluting with 1:1 hexane-EtOAc

Sources & evidence

ORD record
ord-c88a4d3552e14e10a49fb9171487a527
Source dataset
uspto-grants-1999_02
Patent number
US05869488

Reaction notes

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