Diisopropylethylamine → Methyl 6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxylate

Temperature

100 °C

To a screw-cap vial equipped with a magnetic stir bar, methyl 6-bromo-5-fluoropyridine-2-carboxylate (Frontier Scientific, 200.2 mg, 0.8555 mmol) was added followed by 2-(2,6-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Combi-Blocks, 310.2 mg, 1.292 mmol), and bis(tri-tert-butylphosphine)palladium (87.5 mg, 0.171 mmol). The vial was sealed with a PTFE-lined septum, evacuated and backfilled with nitrogen three times. 1,4-Dioxane (3.0 mL) was added via a syringe, followed by DIPEA (0.30 mL, 1.7 mmol) and deoxygenated water (0.1 mL). The mixture was heated at 100° C. for 2 h and was then allowed to cool to room temperature. The mixture was diluted with EtOAc (40 mL), washed with water (40 mL) and brine (40 mL), then dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes) to give the sub-title compound as a white solid (210.2 mg, 92%). LCMS calc. for C13H9F3NO2 (M+H)+: m/z=268.1. found 268.0.

1. customTo a screw-cap vial equipped with a magnetic stir bar
2. customevacuated
3. addition1,4-Dioxane (3.0 mL) was added via a syringe
4. customdeoxygenated water (0.1 mL)
5. temperatureto cool to room temperature
6. additionThe mixture was diluted with EtOAc (40 mL)
7. washwashed with water (40 mL) and brine (40 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes)

ORD record

ord-ff2066b21ba74a838bffd1f19b5b559b

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200004B2