Acetic Acid → (R)-3-methoxymethyl-N-(chloroacetyl)piperidine

Participants

Reaction Steps

To a suspension of (R)-3-methoxymethylpiperidine hydrochloride (6.00 g, 36.3 mmol), sodium acetate (6.55 g, 79.9 mmol) and acetic acid (4.57 ml, 79.9 mmol) in tetrahydrofuran (120 ml) was added dropwise chloroacetyl chloride (3.18 ml, 39.9 mmol) under ice-cooling, and the mixture was stirred overnight at room temperature. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:4) to give (R)-3-methoxymethyl-N-(chloroacetyl)piperidine (6.00 g, yield 80.0%).

Provenance & Evidence