Ethyl Acetate → Tert-butyl 4-[2-(5,7-dioxo-[1,3]dioxolo[4,5-f]isoindol-6-yl) ethyl]piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a 1 L reaction vessel, 52 g (0.27 mol) of [1,3]dioxolo[4,5-f]isoindole-5,7-dione (compound V-1, synthesized according to the method in the references: J. Am. Chem. Soc., 1951, 73, 1371 and J. Am. Chem. Soc., 1963, 85, 473) and 320 ml dimethyl sulfoxide was added, and the mixture was stirred and heated to 60° C., 110 ml solution of 23.4 g (0.42 mol) of potassium hydroxide in ethanol was added after the solid was completely dissolved, the resulting mixture was stirred for 15 min, and then 160 ml solution of 117 g (0.31 mol) of tert-butyl 4-[2-(tosyloxy)ethyl]piperidine-1-carboxylate (compound VI-1, synthesized according to the method disclosed in the PCT application WO2007082731) in dimethyl sulfoxide was added, after addition, the reaction was kept at 60° C. for 5 h until the reaction was completed, 500 ml ethyl acetate and 300 ml water were added, extraction was carried out and the organic layer was collected, dried over sodium sulfate, filtered, the filtrate was concentrated to dry, and 102.2 g crude product was obtained, it was separated by column chromatography, and 72 g compound XI was obtained, with yield of 65.8%. 1H NMR (DMSO-d6): δ 0.90-1.00 (m, 2H), 1.36 (s, 10H), 1.46 (q, 2H, J=7.0 Hz), 1.66 (d, 2H, J=11.9 Hz), 2.62 (br s, 2H), 3.51 (t, 2H, J=7.0 Hz), 3.88 (d, 2H, J=11.5 Hz), 6.24 (s, 2H), 7.32 (s, 2H); MS (ESI): m/z 425 [M+Na]+.

Provenance & Evidence