Tetrahydrofuran → Tert-butyl 4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Participants

Reaction Steps

To a 250 mL round bottom flask containing tert-butyl 4-((2-chloro-N-ethylacetamido)methyl)-4-hydroxypiperidine-1-carboxylate (3.14 g) was added tetrahydrofuran (50 mL). The entire vessel was placed under nitrogen and stirred at room temperature. To this was portionwise added NaH (60% in mineral oil, 2 g, 50.0 mmol). After complete addition, the reaction mixture was stirred at room temperature. After 3 hours, saturated aq sodium bicarbonate (70 mL) was added to the flask (slowly dropwise via pipette at first, then the final 60 mL can be added directly). The solution was transferred to a reparatory funnel containing ethyl acetate (150 mL) and water (50 mL). The organic layer was washed with the aqueous solution, separated, and set aside. The aqueous layer was washed with ethyl acetate (1×50 mL). The combined organic extracts were washed with brine (2×50 mL), separated, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (50-100% ethyl acetate:hexanes) afforded the title compound (1.7 g, 61%). MS(ES)+ m/e 299.5 [M+H]+.

Provenance & Evidence