4-Nitrobenzoic Acid → tert-butyl (8S,9aR)-8-[(4-nitrobenzoyl)oxy]-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl (8R,9aR)-8-hydroxy-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate (50 mg, 0.185 mmol, 1.0 equivalent, Part D), triphenylphosphine (60.6 mg, 0.231 mmol, 1.25 equivalents), and 4-nitrobenzoic acid (46.4 mg, 0.277 mmol, 1.5 equivalents) were dissolved in tetrahydrofuran (1.0 mL), and the resulting solution was cooled to −78° C. Diisopropyl azodicarboxylate (0.043 mL, 0.222 mmol, 1.2 equivalents) was dissolved in tetrahydrofuran (0.5 mL), and the resultant solution was added to the reaction mixture. The reaction mixture was removed from the cooling bath and warmed to room temperature for 0.5 hour. After the addition of 1 drop of saturated sodium bicarbonate, the tetrahydrofuran solution was loaded directly onto 2 sequentially linked 4 g silica gel cartridges, eluted with 50-100% ethyl acetate/heptanes over 20 minutes. The titled compound co-eluted with triphenylphosphine oxide and was used without additional purification (225 mg combined material). 1H NMR (400 MHz, CDCl3) δ ppm 8.28 (d, J=8.9 Hz, 2H), 8.15 (d, J=8.9 Hz, 2H), 5.52 (t, J=4.0 Hz, 1H), 4.53-3.94 (m, 4H), 3.73 (dd, J=14.1, 4.2 Hz, 1H), 3.02 (br s, 1H), 2.78-2.59 (m, 3H), 2.55 (dt, J=13.7, 7.0 Hz, 1H), 2.03-1.91 (m, 1H), 1.47 (s, 9H); MS (ESI+) m/z 419.8 (M+H)+.

Provenance & Evidence