反应详情

A mixture of 2-bromo-1-(2,4-difluorophenyl)ethanone (150 g, 640 mmol, Example #8, Step A), pyrrolidin-2-imine hydrochloride (108 g, 894 mmol) and Na2CO3 (134 mL, 3190 mmol) in DMF (650 mL) was stirred and heated at about 80° C. in a 3 L 3 necked flask for about 24 h. The mixture was cooled to ambient temperature and poured into water (about 5 L). The product was partitioned between EtOAc (800 mL) and the basic aqueous phase. The aqueous layer was extracted with additional EtOAc (3×800 mL). The combined organic extracts were washed with water (4×800 mL), dried over MgSO4 and filtered through a pad of Florisil® (2″ depth×3″ diameter). The pad was washed with EtOAc (4×250 mL) and the filtrate was concentrated to dryness under reduced pressure to yield the title compound as a solid (98.6 g, 70%): LC/MS (Table 1, Method a) Rt=2.72 min; MS m/z: 221.0 (M+H)+.

1. customThe product was partitioned between EtOAc (800 mL)
2. extractionThe aqueous layer was extracted with additional EtOAc (3×800 mL)
3. washThe combined organic extracts were washed with water (4×800 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered through a pad of Florisil® (2″ depth×3″ diameter)
6. washThe pad was washed with EtOAc (4×250 mL)
7. concentrationthe filtrate was concentrated to dryness under reduced pressure