Methyl iodide → 1-Benzyl-3,5-dimethylpiperidin-4-one

HRID 1726452Notes

Reaction equation

HRID 1726452 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][Si](C)(C)[N-][Si](C)(C)C.[Li+].IC>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH:12]([CH3:16])[C:11](=[O:14])[CH:10]([CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 5609651-Benzyl-3-methyl-4-piperidoneHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 222789201-Benzyl-3,5-dimethylpiperidin-4-oneYield 31.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 1-benzyl-3-methyl-piperidin-4-one (4.06 g, 20 mmol) in anhydrous THF (20 mL) was added lithium hexamethyldisilazide (21 mL, 21 mmol of a 1.0 M solution THF). After being stirred at −78° C. for 30 min, a solution of iodomethane (1.31 mL, 21 mmol) in THF (5 mL) was added into the reaction mixture. The resultant solution was stirred at 25° C. for 2 h and quenched with water. The aqueous layer was extracted with CH2Cl2. The organic extracts were combined, washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude product. The crude material was purified by flash column chromatography (hexane/EtOAc) to provide 1.37 g (31.5% yield) of 1-benzyl-3,5-dimethyl-piperidin-4-one.

Workup

  1. customquenched with water
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customThe crude material was purified by flash column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-65578f1b854140488c00112e3e85a0f3
Source dataset
uspto-grants-2009_02
Patent number
US07491827B2

Reaction notes

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