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

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Reaction Steps

A mixture of trimethylsulfoxonium iodide (65.2 g, 29.6 mmol) and anhydrous DMSO (300 ml) was stirred at room temperature for 1 hour under a nitrogen atmosphere. The reaction was then cooled to 0° C. and NaH (60% in mineral oil) (14.2 g, 35.5 mmol) was added in small portions over the course of 1 hour. The reaction mixture was allowed to warm to room temperature and stirred for 4 hours. The reaction mixture was then cooled to 0° C., tert-butyl 4-oxo-1-piperidinecarboxylate (59.0 g, 29.6 mmol) added, then allowed to react at room temperature for 16 hours. The reaction mixture was then poured onto 1.2 liters of ice water and extracted with ether (4×400 ml). The organic layers were washed with water (2×500 ml) and brine (2×500 ml). The organic extract was dried with Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (SiO2, 5% EtOAc in hexanes to 40% EtOAc in hexanes) to afford the product as white crystalline solid (35.3 g, 56%). M.p.=48-50° C.; 400 MHz 1H NMR (CDCl3) δ: 3.77-3.68 (m, 2H), 3.45-3.36 (m, 2H), 2.68 (s, 2H), 1.83-1.74 (m, 2H), 1.5-1.4 (m, 11H); LCMS: 214 [M+H].

Provenance & Evidence