反应详情

温度

115 °C

To a 20 mL microwave vial were added methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (0.80 g, 3.41 mmol), (2,3-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl)trimethylsilane (1.28 g, 4.09 mmol), sodium carbonate (Na2CO3; 0.36 g, 3.41 mmol), and PdCl2(PPh3)2 (0.24 g, 0.34 mmol). Subsequently, CH3CN (5.7 mL) and H2O (5.7 mL) were added, and the reaction vial was sealed and heated in a Biotage microwave to 115° C. for 20 min. The reaction mixture was cooled to room temperature and diluted with EtOAc (10 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (2×2 mL). The organic extracts were combined, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified using a Teledyne ISCO purification system with a gradient eluent system of EtOAc and hexanes to yield methyl 4-amino-6-(2,3-difluoro-4-(trimethylsilyl)phenyl)-5-fluoro-3-methoxypicolinate (0.99 g, 75%) as a white solid: mp 123-125° C.; 1H NMR (400 MHz, CDCl3) δ 7.32 (ddd, J=7.6, 5.5, 1.1 Hz, 1H), 7.20 (ddd, J=7.7, 4.5, 1.4 Hz, 1H), 4.60 (s, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 0.41-0.28 (m, 9H); 19F NMR (376 MHz, CDCl3) δ −127.39, −127.45, −127.46, −137.48, −137.56, −140.78, −140.85, −140.86, −140.92; ESIMS m/z 383.20 ([M−H]−).

1. customthe reaction
2. customvial was sealed
3. temperatureThe reaction mixture was cooled to room temperature
4. customThe organic layer was separated
5. extractionthe aqueous phase was extracted with EtOAc (2×2 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified
10. customa Teledyne ISCO purification system with a gradient eluent system of EtOAc and hexanes