Dimethylformamide → 5-(3,4-Difluorophenyl)-2,3-dimethyl-benzoic acid

Temperature

100 °C

To a mixture of 5-bromo-2,3-dimethyl-benzoic acid (500 mg, 2.18 mmol, 1.0 eq), (3,4-difluorophenyl)boronic acid (378.6 mg, 2.40 mmol, 1.1 eq) and Na2CO3 (693 mg, 6.54 mmol, 3.0 eq) in a mixture of EtOH (2.5 mL), DMF (10 mL) and H2O (2.5 mL) was added Pd(PPh3)4 (126 mg, 0.11 mmol, 0.05 eq) under nitrogen. The mixture was stirred at 100° C. overnight. After cooling to room temperature, water was added and the diluted reaction mixture filtered through celite. The aqueous layer was extracted with EtOAc and the organic extract was discarded. The remaining aqueous layer was acidified to pH 2 by addition of 3M HCl. The resulting mixture was extracted with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give the title compound as a white solid (400 mg, 70%).

1. temperatureAfter cooling to room temperature
2. customthe diluted reaction mixture
3. filtrationfiltered through celite
4. extractionThe aqueous layer was extracted with EtOAc
5. extractionthe organic extract
6. additionThe remaining aqueous layer was acidified to pH 2 by addition of 3M HCl
7. extractionThe resulting mixture was extracted with EtOAc
8. washthe combined organic extracts were washed with water and brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. customevaporated in vacuo

ORD record

ord-3415f8a2e6b6415c8fabd44d6304c278

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249085B2