Triethylamine → tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate

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Reaction Steps

Add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (46.07 mmol) and cesium carbonate (115.2 mmol) to a solution of acetonitrile (200 mL). After stirring at room temperature for 20 minutes, add 4-bromobutyne (69.1 mmol) and heat the mixture to reflux with stirring overnight. Cool to room temperature and dilute with ethyl acetate (200 mL). Filter the reaction through a glass frit rinsing with ethyl acetate (2×100 mL). Concentrate the crude mixture under reduced pressure, then add ethyl acetate (200 mL) and wash the organics with water (200 mL) and brine (200 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure to yield crude tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate (13.6 g, 44.4 mmol): MS (m/z): 307.2 (M+H). To a round bottom flask under nitrogen, add tert-butyl 4-but-3-ynyl-4,9-diazaspiro[5.5]undecane-9-carboxylate (44.4 mmol), triethylamine (4.44 mmol), zirconocene chloride (4.44 mmol), and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (48.8 mmol). Heat this mixture to 60° C. for 3 hours, then stir overnight at room temperature. Dissolve the mixture in dichloromethane (20 mL) and purify by flash chromatography (330 g silica gel cartridge) eluting with 15-85% ethyl acetate in hexanes to yield the final title compound, tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate (29.9 mmol) as a light yellow oil: MS (m/z): 435.2 (M+H).

Provenance & Evidence