Ethyl 4-oxo-1-piperidinecarboxylate → Ethyl 4-hydroxy-4-methylpiperidine-1-carboxylate

HRID 1050542Notes

Reaction equation

HRID 1050542 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH3:13][Mg+].[Br-]>CCOCC>[OH:1][C:2]1([CH3:13])[CH2:3][CH2:4][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 178418689HCID 178418689, compound

Product 1

HCID 55277039Ethyl 4-hydroxy-4-methylpiperidine-1-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

At −30° C. and under N2 atmosphere, to a solution of ethyl 4-oxopiperidine-1-carboxylate (282) (6.0 g, 35.1 mmol) in anhydrous Et2O (100 mL) was added MeMgBr (3.0 M, 14 mL, 42.1 mmol). The resulting mixture was stirred at 0° C. for 2 hours before being quenched with aqueous NH4Cl solution. The mixture was extracted with DCM (30 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, concentrated in vacuo and subjected to silica flash column chromatography using 0 to 50% EtOAc in PE (petroleum ether) to isolate ethyl 4-hydroxy-4-methylpiperidine-1-carboxylate (283) (4 g, 61%) as an oil.

Workup

  1. custombefore being quenched with aqueous NH4Cl solution
  2. extractionThe mixture was extracted with DCM (30 mL×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2959e5e079ed4b269ceb13955cedebda
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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