Hydrochloric Acid → Tert-butyl 4-[2-(5-methylene-7-oxo-[1,3]dioxolo[4,5-f]isoindol-6-yl)ethyl]piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a reaction vessel, 75 g (0.19 mol) compound XI and 500 ml tetrahydrofuran were added while stirring under nitrogen, The mixture was cooled to 0-10° C., 400 ml 1.2N methylmagnesium iodide/ethyl ether solution was slowly added into the reaction vessel, the reaction was kept for 1 h, a minor amount of water was added until there was no bubble formed, concentrated hydrochloric acid was added to adjust the pH to acidic, the reaction was kept for 15 min, 500 ml ethyl acetate and 300 ml water were added, extracted, washed, the organic layer was collected, dried over sodium sulfate, filtered, the filtrate was concentrated to a minor amount, petroleum ether was added, solid was precipitated out, filtered, dried, and 47.6 g compound IX-1 was obtained, with yield of 63.8%. H NMR (DMSO-d6): δ 0.95-1.05 (m, 2H), 1.38 (s, 10H), 1.48 (q, 2H, J=7.0 Hz), 1.71 (d, 2H, J=12.2 Hz), 2.65 (br s, 2H), 3.70 (t, 2H, J=7.2 Hz), 3.90 (d, 2H, J=11.6 Hz), 4.95 (s, 1H), 5.34 (s, 1H), 6.17 (s, 2H), 7.15 (s, 1H), 7.53 (s, 1H); MS (ESI): m/z 423 [M+Na]+.

Provenance & Evidence