Acetonitrile → Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trifluoromethyl)phenyl)picolinate

Temperatur

115 °C

To a 5 mL microwave vial was added methyl 4-amino-6-chloro-5-fluoropicolinate (500 mg, 2.44 mmol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (851 mg, 2.93 mmol), potassium fluoride (KF; 369 mg, 6.35 mmol), and PdCl2(PPh3)2 (172 mg, 0.24 mmol). Subsequently, CH3CN (3.0 mL) and H2O (3.0 mL) were added, and the reaction vial was sealed and heated in a Biotage microwave at 115° C. for 20 min. The reaction mixture was cooled to room temperature and diluted with EtOAc (5 mL). The layers were separated and the aqueous phase was extracted with EtOAc (2×2 mL). The organic extracts were combined, dried (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 the title compound as a yellow solid (570 mg, 70%): 1H NMR (400 MHz, DMSO-d6) δ 7.94 (dt, J=12.3, 6.2 Hz, 3H), 7.52 (d, J=6.4 Hz, 1H), 6.80 (s, 2H), 3.86 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −59.96, −59.99, −115.69, −144.18, −144.20; ESIMS m/z 333.21 ([M+H]+).

1. customthe reaction
2. customvial was sealed
3. temperatureThe reaction mixture was cooled to room temperature
4. customThe layers were separated
5. extractionthe aqueous phase was extracted with EtOAc (2×2 mL)
6. dry with materialdried (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

ORD-Eintrag

ord-c8fca37c56124f79ab5b82cb5ac7327e

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08754229B2