反应详情

温度

60 °C

Pd(dppf)Cl2 (484 mg, 0.59 mmol) was added to a mixture of ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate, T2, (2.20 g, 4.94 mmol), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole (2.01 g, 7.41 mmol), and potassium phosphate (3.95 g, 14.8 mmol) in 2-methyltetrahydrofuran (200 mL) and deionized water (40 mL). The reaction was heated to 60° C. and was vigorously stirred at this temperature overnight. The reaction was diluted with EtOAc (100 mL) and water (100 mL) and was filtered through a celite pad (˜1 inch). The filter pad was washed with EtOAc (100 mL) and the filtrates were combined. The aqueous layer was separated and was extracted with EtOAc (2×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated. The crude material was purified via flash chromatography using a Varian SF25-40 g column and an eluent of EtOAc in hexanes (30-100%) to afford the title compound as a yellow solid (1.54 g, 67.4%). MS (LCMS) m/z 463.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (t, 3H) 1.62 (s, 3H) 2.18-2.32 (m, 1H) 2.52-2.66 (m, 1H) 3.16 (s, 3H) 3.92-4.07 (m, 2H) 4.08-4.24 (m, 2H) 6.59 (d, J=7.81 Hz, 1H) 7.72-7.84 (m, 2H) 8.10 (d, J=6.63 Hz, 1H) 8.12-8.17 (m, 2H) 8.18 (s, 2H).

1. filtrationwas filtered through a celite pad (˜1 inch)
2. washThe filter pad was washed with EtOAc (100 mL)
3. customThe aqueous layer was separated
4. extractionwas extracted with EtOAc (2×100 mL)
5. washThe combined organics were washed with brine (100 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude material was purified via flash chromatography