反应详情

温度

22.5 °C

To a stirred solution of 2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (93.5 g, 425 mmol) in DMF (550 mL), NIS (105 g, 467 mmol) was added portionwise over about 1 h, maintaining the temperature at about 20-25° C. with an ice-water bath. After the final addition, the reaction suspension was stirred for about 2 h. After a total of about 3 h from the start of addition of the NIS, the reaction mixture was poured into ice water (4 L) and was stirred at about 15-20° C. for about 15 min before the addition of a 10% solution of Na2S2O3 (500 mL). The resulting solution was stirred for about 1 h. The tan colored solid was collected by vacuum filtration, washed with water (5×200 mL), and dried overnight at room temperature. The solid was stirred with ether (300 mL), filtered, and washed with additional portions of ether (3×30 mL). This ether trituration process was repeated before the solid was dried in a vacuum oven at about 50-60° C. to give the title compound as a powdery solid (91.4 g, 52%): LC/MS (Table 1, Method h) Rt=1.40 min; MS m/z: 347.0 (M+H)+.

1. additionAfter the final addition
2. stirringThe resulting solution was stirred for about 1 h
3. filtrationThe tan colored solid was collected by vacuum filtration
4. washwashed with water (5×200 mL)
5. customdried overnight at room temperature
6. stirringThe solid was stirred with ether (300 mL)
7. filtrationfiltered
8. washwashed with additional portions of ether (3×30 mL)
9. customwas dried in a vacuum oven at about 50-60° C.