Methyl iodide → tert-Butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate

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Reaction Conditions

Reaction Steps

4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (5 g, 25 mmol) was dissolved in tetrahydrofuran (100 mL) and the resulting solution was cooled to 0° C. Sodium hydride (60% in mineral oil, 2.10 g, 53 mmol) was added to the cooled solution in a single portion, and the resulting cloudy mixture was allowed to stir 10 min. Methyl iodide was subsequently added and the mixture was allowed to warm to room temperature over several hours. Stirring continued over night (12 h). The light orange mixture was concentrated under reduced pressure. The residue was partitioned between ether and water. The aqueous phase was back-extracted with additional ether. The combined extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated to a pale yellow solid. The solid was triturated with 4% ethyl acetate in hexanes (50 mL) to afford 3,3-dimethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester as a cream-colored solid (1.8 g, 32%). 1H-NMR (CDCl3, 300 MHz) δ 3.73 (t, 2H), 3.43 (br s, 2H), 2.49 (t, 2H), 1.49 (s, 9H), 1.13(s, 6H).

Provenance & Evidence