TERT-BUTYL 6-BROMO-4-OXO-3,4-DIHYDRO-1'H-SPIRO[1,3-BENZOXAZINE-2,4'-PIPERIDINE]-1'-CARBOXYLATE synthesis

Yield:690632-05-4 63%

Reaction Conditions:

with pyrrolidine at 72; for 2 h;Microwave irradiation;

Steps:

Three batches of 5-bromo salicylamide (4, 5.00g each, 23.1mmol), N-Boc-piperidin-4-one (3.45g, 17.3mmol) and pyrrolidine (1.64g, 23.1mmol) were heated in different flasks at 72°C under MW irradiation for 1h. Further N-Boc-piperidin-4-one (3.45g, 17.3mmol) was added and the mixtures were heated for 1h at 72°C. The resulting precipitates were collected by filtration and washed with MeOH to give the spirocycle 5 (17.2g, 63%) as a white solid. ¹H NMR (300MHz, DMSO-d₆): δ=8.86 (s, 1H), 7.82 (d, J=2.35Hz, 1H), 7.69 (dd, J=8.66, 2.49Hz, 1H), 7.06 (d, J=8.80Hz, 1H), 3.64-3.88 (m, 2H), 3.02-3.21 (m, 2H), 1.91-2.10 (m, 2H), 1.63-1.78 (m, 2H), 1.40ppm (s, 9H).

References:

Thaler, Florian;Varasi, Mario;Abate, Agnese;Carenzi, Giacomo;Colombo, Andrea;Bigogno, Chiara;Boggio, Roberto;Zuffo, Roberto Dal;Rapetti, Daniela;Resconi, Anna;Regalia, Nickolas;Vultaggio, Stefania;Dondio, Giulio;Gagliardi, Stefania;Minucci, Saverio;Mercurio, Ciro [European Journal of Medicinal Chemistry,2013,vol. 64,p. 273 - 284]