Diethyl Malonate → Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioate

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Reaction Steps

Diethyl malonate (10.4 g, 65 mmol) was added to a solution of sodium ethoxide (4.42 g, 65 mmol) in ethanol (75 mL). 1-(tert-Butoxycarbonyl)-4-[(p-toluenesulfonyloxy)methyl]piperidine (25 g, 68 mmol), prepared as in Example 1, Step (a), was added and the mixture was heated at reflux for 4 hours. The mixture was cooled and partitioned between ethyl acetate and water. The ethyl acetate layer was separated, washed with water and then brine, dried over sodium sulfate, and evaporated. Purification of the residue by silica gel chromatography (25% ethyl acetate-hexane) gave 1-(tert-butoxycarbonyl)-4-[2,2-di(ethoxycarbonyl)ethyl]piperidine (16 g, 45 mmol) as an oil.

Provenance & Evidence