Potassium Carbonate → 1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone

HRID 1798926Notes

Reaction equation

HRID 1798926 reaction equation
Cl.[CH3:2][C:3]1([NH2:9])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].[I-].C([N+]1(C)[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)C.C([O-])(O)=O.[Na+]>C(O)C.O.C(O)C.O>[CH3:2][C:3]1([N:9]2[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 110975681-Ethyl-1-methyl-4-oxopiperidin-1-ium iodideHCID 184373724-Methyloxan-4-amine hydrochloride

Product 1

HCID 596832511-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinoneYield 39.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
85 °C

Procedure

A stirred solution of 4-methyltetrahydro-2H-pyran-4-amine hydrochloride (D11) (640 mg, 4.22 mmol) in ethanol (20 mL) and H2O (10 mL) at room temperature was treated with potassium carbonate (417 mg, 3.02 mmol) and the stirring was maintained for 10 min under argon. The mixture was then heated to 85° C. and a solution of 1-ethyl-1-methyl-4-oxopiperidinium iodide (D13, 1.11 g, 4.11 mmol) in a mix of ethanol/H2O (8 mL, 1:1) was added over 15 min. The mixture was then refluxed for 2 extra hours. The mixture was then cooled to room temperature and poured onto an aqueous saturated solution of NaHCO3. The aqueous obtained was extracted with DCM (3×). Organics were combined and washed with H2O (1×), dried over Na2SO4, filtered and concentrated under vacuum. The crude product was then purified via chromatography (silica, DCM to 5% MeOH/95% DCM). The title compound (D12) (322 mg, 37%) was obtained as a yellow solid.

Workup

  1. temperaturethe stirring was maintained for 10 min under argon
  2. additionwas added over 15 min
  3. temperatureThe mixture was then refluxed for 2 extra hours
  4. temperatureThe mixture was then cooled to room temperature
  5. customThe aqueous obtained
  6. extractionwas extracted with DCM (3×)
  7. washwashed with H2O (1×)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThe crude product was then purified via chromatography (silica, DCM to 5% MeOH/95% DCM)

Sources & evidence

ORD record
ord-d1538041b535456db30bfee7568116d8
Source dataset
uspto-grants-2013_01
Patent number
US08344000B2

Reaction notes

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