Sodium hydride → tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

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Reaction Steps

A mixture of trimethylsulfoxonium iodide (50.2 mmol) and anhydrous dimethyl sulfoxide (DMSO) (50 mL) was stirred at room temperature for 1 h. The reaction was then cooled to 0° C. and 60% sodium hydride in mineral oil (60.2 mmol) was added in small portions over several minutes. The reaction was allowed to warm to room temperature and stirred for 2 h. The resulting white slurry was cooled to 0° C. then treated with solid 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (50.2 mmol) in one portion. The ice bath was removed and stirring continued at room temperature for 18 h. Ice cold water (150 mL) was added and the mixture was extracted into diethyl ether (3×). The extracts were washed with brine, dried (sodium sulfate) then evaporated under reduced pressure to a yellow oil. The oil was dissolved in ethyl acetate, treated with silica powder (˜20 g), and evaporated to dryness. This was placed on a short pad of silica in a sintered glass funnel and washed with hexanes (500 mL; the filtrate was discarded). The silica pad was then washed with 2:1 hexanes/ethyl acetate. The filtrate was evaporated in vacuo to give the title product (6.40 g, 57% yield) as a pale yellow oil that solidified upon standing. MS(ES)+ m/e 214.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 11 H) 1.72-1.87 (m, 2 H) 2.69 (s, 2H) 3.36-3.50 (m, 2 H) 3.63-3.83 (m, 2 H).

Provenance & Evidence