1-Benzyl-4-piperidone → 1-Benzyl-4-methylpiperidin-4-ol

HRID 1066990Notes

Reaction equation

HRID 1066990 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][Li]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([CH3:15])([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 192201-Benzyl-4-piperidoneHCID 178418348HCID 178418348, compound

Product 1

HCID 108459131-Benzyl-4-methylpiperidin-4-olYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-benzyl-4-piperidone (5.6 mL, 30.0 mmol) in 50 mL THF was added a solution of methyllithium in THF (24.0 mL, 36 mmol) dropwise at 0° C. over 15 min. The reaction mixture was allowed to warm to room temperature over 3 h and then quenched with 30 mL of sat. NH4Cl solution. The organic layer was extracted with diethyl ether (2×100 mL) and the combined organic layer was washed with brine (100 mL). The organic layer was separated, dried over Na2SO4, filtered and the solvent was removed in vacuo to obtain yellow gum. It was purified by column chromatography over silica gel with 9:1 EtOAc-MeOH as the eluting system to obtain 1-benzyl-4-methyl-4-piperidinol as a yellow thick oil (3.6 g, 59% yield).

Workup

  1. customquenched with 30 mL of sat. NH4Cl solution
  2. extractionThe organic layer was extracted with diethyl ether (2×100 mL)
  3. washthe combined organic layer was washed with brine (100 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. customto obtain yellow gum
  9. customIt was purified by column chromatography over silica gel with 9:1 EtOAc-MeOH as the eluting system

Sources & evidence

ORD record
ord-f0bd337f7f4f4e7a9d43f39f13e92bc2
Source dataset
uspto-grants-2001_06
Patent number
US06245773B1

Reaction notes

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