反应详情

温度

80 °C

Into an oven-dried flask were charged 3-bromo-2-fluoropyridine (1.3 g, 7.39 mmol), Pd catalyst (0.181 g, 0.222 mmol), copper(i) iodide (0.084 g, 0.443 mmol), and DMA (10 mL). The resulting mixture was degassed with alternating vacuum/nitrogen purges. The (1-(tert-butoxycarbonyl)pyrrolidin-3-yl)zinc(II) iodide (3.75 g, 10.34 mmol) solution from previous step was filtered into the mixture. It was degassed one more time and then heated to 80° C. with stirring for 16 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and 1 N NH4Cl. The aqueous layer was back extracted with EtOAc (2×) and the combined EtOAc layer was washed once again with 1 N NH4Cl, then with brine, dried (Na2SO4) and concentrated. The crude material as chromatography through a Redi-Sep pre-packed silica gel column (120 g), eluting with a gradient of 0% to 40% EtOAc in hexane, to provide tert-butyl 3-(2-fluoropyridin-3-yl)pyrrolidine-1-carboxylate as dark-red oil. [M−56]=211.2.

1. customThe resulting mixture was degassed
2. customIt was degassed one more time
3. temperatureAfter cooling to RT
4. customthe reaction mixture was partitioned between EtOAc and 1 N NH4Cl
5. extractionThe aqueous layer was back extracted with EtOAc (2×)
6. washthe combined EtOAc layer was washed once again with 1 N NH4Cl
7. dry with materialwith brine, dried (Na2SO4)
8. concentrationconcentrated
9. washThe crude material as chromatography through a Redi-Sep pre-packed silica gel column (120 g), eluting with a gradient of 0% to 40% EtOAc in hexane