4-Methylmorpholine → N-(tert-butoxycarbonyl)piperidine

Participants

Reaction Steps

Part A: To a solution of N-BOC-isoponic acid (4.0 g, 17.4 mmol) in dimethylacetamide (30 mL) were added N-methylmorpholine (Aldrich, 5.7 mL, 52.2 mmol), 3,5-dimethylpiperadine (70% cis, Aldrich, 3.5 mL, 26.1 mmol), N-hydroxybenzotriazole hydrate (Aldrich, 2.8 g, 20.9 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (Sigma, 5.0 g, 26.1 mmol). The mixture was stirred overnight (about 18 hr) at ambient temperature. To work up, the solvent was removed and the residue was taken up in ethyl acetate (300 mL) then washed with 5% KHSO4 aq (1×100 ml), saturated K2CO3 aq (1×100 mL), and brine (1×100 mL). After drying over Na2SO4, the organic layer was filtered and concentrated to afford the BOC-piperidine as a tan oil that slowly crystallized (5.4 g, 96% yield). 1H NMR showed the desired compound existing as both the cis- and trans-isomers.

Provenance & Evidence