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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence