反应详情

To a 5-mL microwave safe vial were added methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (0.400 g, 1.705 mmol), (2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (0.690 g, 2.344 mmol), KF (0.297 g, 5.11 mmol), and PdCl2(PPh3)2 (0.120 g, 0.170 mmol). A mixture of H2O (1 mL) and CH3CN (2 mL) was added, and the reaction vial was capped and placed in a Biotage Initiator microwave reactor for 20 min at 115° C. with external infrared (IR)-sensor temperature monitoring from the side of the vessel. Upon cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (25 mL) and H2O (25 mL), and the organic layer was filtered through a cotton plug. An additional extraction using EtOAc (25 mL) was combined with the CH2Cl2 and dried over Na2SO4 (50 g). Following filtration of the combined organics through a cotton plug and concentration on a rotary evaporator, the residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc to yield the title compound as a light pink oil (333 mg, 53%): 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=7.6 Hz, 1H), 7.55 (d, J=9.8 Hz, 1H), 7.46 (dd, J=7.6, 5.9 Hz, 1H), 4.57 (s, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 0.33 (s, 9H); 19F NMR (376 MHz, CDCl3) δ −100.72, −140.12; ESIMS m/z 367 ([M+H]+).

1. additionwas added
2. customthe reaction vial was capped
3. filtrationthe organic layer was filtered through a cotton plug
4. extractionAn additional extraction
5. dry with materialdried over Na2SO4 (50 g)
6. filtrationfiltration of the
7. concentrationcombined organics through a cotton plug and concentration
8. customon a rotary evaporator
9. customthe residue was purified
10. customa Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc