反应详情

温度

80 °C

In an oven-dried flask were charged 2-fluoro-3-iodopyrazine (0.829 g, 3.70 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(ii) complex with dichloramethane (0.091 g, 0.111 mmol), copper(i) iodide (0.042 g, 0.222 mmol), and DMA (3 mL). The resulting mixture was degassed with alternating vacuum/nitrogen purges. The (1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) iodide (1.951 g, 5.18 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 treated with methyl bert-butylether (13 ml) and 1 N NH4Cl (13 ml). The organic layer was partitioned between Teac and 1 N NH4Cl and the aqueous layer was back extracted with Teac (2×). The combined organic layer was washed with water, brine, dried (Na2SO4) and concentrated. The crude material was chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 20% Teac in hexane, to provide tert-butyl 4-(3-fluoropyrazin-2-yl)piperidine-1-carboxylate as orange oil. MS (ESI, pos. ion) m/z: 226.0 (M-56).

1. customThe resulting mixture was degassed
2. customIt was degassed one more time
3. temperatureAfter cooling to RT
4. additionthe reaction mixture was treated with methyl bert-butylether (13 ml) and 1 N NH4Cl (13 ml)
5. customThe organic layer was partitioned between Teac and 1 N NH4Cl
6. extractionthe aqueous layer was back extracted with Teac (2×)
7. washThe combined organic layer was washed with water, brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. washeluting with a gradient of 0% to 20% Teac in hexane