Water → Methyl 2-chloro-4-fluoro-5-(pyridin-2-yl)benzoate

To a solution of methyl 2-chloro-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (212 mmol) in THF (400 mL), was added 2-bromopyridine (33.4 g, 211 mmol), potassium carbonate (117 g, 848 mmol) and water (64 mL). The mixture was degassed with argon for 30 minutes. To this mixture was added tetrakis(triphenylphosphine)palladium (12.2 g, 10.6 mmol) and the mixture heated at reflux for 1.5 h. The mixture was cooled to room temperature and filtered through Celite, washing with EtOAc (1.2 L) and water (800 mL). The filtrate was diluted with saturated aqueous brine solution (200 mL) and the aqueous layer separated and extracted with EtOAc (600 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography over silica gel, eluting with EtOAc:hexane (3:17 to 1:4) and concentrated in vacuo to a slurry, which was diluted with heptane (100 mL) and cooled to 0° C. The solid was collected by filtration to afford the title compound (37.6 g, 67%).

1. customThe mixture was degassed with argon for 30 minutes
2. temperaturethe mixture heated
3. temperatureat reflux for 1.5 h
4. filtrationfiltered through Celite
5. washwashing with EtOAc (1.2 L) and water (800 mL)
6. additionThe filtrate was diluted with saturated aqueous brine solution (200 mL)
7. customthe aqueous layer separated
8. extractionextracted with EtOAc (600 mL)
9. dry with materialThe combined organic layers were dried (MgSO4)
10. concentrationconcentrated in vacuo
11. customThe residue was purified by column chromatography over silica gel
12. washeluting with EtOAc:hexane (3:17 to 1:4)
13. concentrationconcentrated in vacuo to a slurry, which
14. additionwas diluted with heptane (100 mL)
15. temperaturecooled to 0° C
16. filtrationThe solid was collected by filtration

ORD record

ord-16d79907aacb4068a201e86aa840e640

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328096B2