反应详情

tert-Butyl(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamate 1m (20.0 g, 39.6 mmol) was dissolved in 300 mL of anhydrous ethanol, and N-bromosuccinimide (14.1 g, 79.2 mmol) was then added to the solution. After stirring for an hour, potassium carbonate (10.9 g, 79.2 mmol) and di-tert-butyl dicarbonate (8.6 g, 39.6 mmol) were added to the mixture, and the mixture was stirred for another one hour. The reaction mixture was filtered through a pad of coarse silica gel, and then the filtrate was concentrated under reduced pressure. The resulting residues were purified by silica gel column chromatography with system B as eluant to obtain the title compound tert-butyl (R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamate 1n (20.0 g, yield 86%) as a white solid. 1HNMR (400 MHz, CDCl3, ppm): δ 7.063 (m, 1H), 6.88 (m, 1H), 4.72 (s, 1H), 4.56 (s, 1H), 4.13 (m, 3H), 3.88 (m, 2H), 2.94 (m, 2H), 2.62 (m, 2H), 1.36 (s, 9H).

1. stirringthe mixture was stirred for another one hour
2. filtrationThe reaction mixture was filtered through a pad of coarse silica gel
3. concentrationthe filtrate was concentrated under reduced pressure
4. customThe resulting residues were purified by silica gel column chromatography with system B as eluant