tert-Butyl 4-oxopiperidine-1-carboxylate → 1-Boc-4-methyl-piperidin-4-OL

HRID 1402243Notes

Reaction equation

HRID 1402243 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:15][Mg]Br>C(OCC)C>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][C:11]([OH:14])([CH3:15])[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

4

Reactant 2

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 227308121-Boc-4-methyl-piperidin-4-OLYield 62.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 1-Boc-4-piperidone (10.0 g, 50.0 mmol) in diethyl ether (100 mL) at 0° C. was added methylmagnesium bromide (3.0 M in Et2O, 22.3 mL, 67.0 mmol) maintaining the temperature below +10° C. The reaction mixture was allowed to warm to RT over 1 h. The reaction was quenched by addition of sat. aq. NH4Cl solution, then the mixture was extracted with diethyl ether (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-100% EtOAc in cyclohexane, to give the title compound (6.76 g, 62%). 1H NMR (400 MHz, CDCl3): 1.26 (3H, s), 1.45 (9H, s), 1.48-1.62 (4H, m), 3.15-3.32 (2H, m), 3.70 (2H, d, J 12.5).

Workup

  1. temperaturemaintaining the temperature below +10° C
  2. customThe reaction was quenched by addition of sat. aq. NH4Cl solution
  3. extractionthe mixture was extracted with diethyl ether (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-c92c40584ce24e99a78636521ef34529
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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