2,4-Piperadinedione

845267-78-9

50607-30-2

The general procedure for the synthesis of 2,4-piperidinediones from tert-butyl 2,4-dipiperidone-1-carboxylate was as follows: at 0 °C and under nitrogen protection, Boc-β-alanine (25 g, 132 mmol), Meldrum acid (20.9 g, 145 mmol), and 4-dimethylaminopyridine (DMAP, 24.2 g, 198 mmol) were dissolved in 700 mL of anhydrous dichloromethane (DCM). To this solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 30.4 g, 158 mmol). The reaction mixture was slowly warmed to room temperature and stirred overnight. After completion of the reaction, the reaction mixture was washed with 5% KHSO4 aqueous solution (0.5 L x 4). The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product [tert-butyl [3-(2,2-dimethyl-4,6-dioxo-[1,3]dioxol-5-yl)-3-oxo-propyl]-carbamate. The crude product was dissolved in 600 mL of ethyl acetate and refluxed for 4 hours. It was concentrated under reduced pressure to a volume of about 150 mL and subsequently crystallized at 4°C overnight. The solid was collected by filtration and washed with cold ethyl acetate to afford 18.4 g (65% yield) of 2,4-piperidinedione.1H NMR (400 MHz, DMSO-D6) δppm: 1.44 (s, 9H), 2.44 (m, 2H), 3.71 (m, 2H), 4.95 (s, 1H), 11.2 (bs, 1H). The resulting product was converted quantitatively to piperidine-2,4-dione by dissolving in dichloromethane and treating with trifluoroacetic acid for 3 h at room temperature.