Hydrochloric Acid → 3-Oxa-8-azabicyclo(3.2.1)octane hydrochloride

Participants

Reaction Steps

To a suspension of sodium hydride (60% dispersion in mineral oil) (0.284 g, 7.10 mmol) in N,N-Dimethylformamide (5 mL), cooled in an ice bath under argon, was added dropwise a solution of 1,1-dimethylethyl 2-(hydroxymethyl)-5-({[(4-methylphenyl)sulfonyl]oxy}methyl)-1-pyrrolidinecarboxylate (Intermediate 26, 2.28 g, 5.91 mmol) in N,N-Dimethylformamide (10 mL). The reaction was allowed to warm to room temperature and stirred for 5 hours. The reaction was cooled in an ice-water bath before the addition of sat. NH4Cl (30 mL) and water (30 mL). The mixture was extracted with diethyl ether (3×60 mL). The ether layers were combined, washed with water:brine (1:1, 2×60 mL), passed through a hydrophobic frit and the solvent removed to yield a colourless gum, which was dried under vacuum for 18 hours to yield a white solid. The crude intermediate was dissolved in 1,4-Dioxane (5 mL) before the addition of HCl (4M in 1,4-dioxane) (14.8 mL, 59.1 mmol). The reaction was stirred at room temperature for 3 hours then the solvent was removed under vacuum to yield the title compound as a white solid (904 mg).

Provenance & Evidence