Carbon Dioxide → 4-Bromo-2-fluoro-3-methoxybenzoic acid

Temperature

0 °C

n-BuLi (17.0 mL, 42.5 mmol) was added dropwise to the solution of NH(i-Pr)2 (4.50 g, 44.5 mmol) in 70 mL of THF at −70° C. The mixture was stirred at 0° C. for 15 minutes and then cooled to −70° C. again. The solution of 1-bromo-3-fluoro-2-methoxybenzene (8.30 g, 40.5 mmol, in 30 mL of THF) was added dropwise. The resulting mixture was stirred at −70° C. for 1 hour then poured into fresh dry ice and stirred overnight. The mixture was diluted with 1 L of ether and washed with water twice. The combined water layer was washed with ether then acidified to pH=2 with hydrochloric acid and extracted with EtOAc twice. The combined EtOAc layer was washed with brine, dried over anhydrous Na2SO4 and concentrated to give 4-bromo-2-fluoro-3-methoxybenzoic acid.

1. temperaturecooled to −70° C. again
2. stirringThe resulting mixture was stirred at −70° C. for 1 hour
3. stirringstirred overnight
4. washwashed with water twice
5. washThe combined water layer was washed with ether
6. extractionextracted with EtOAc twice
7. washThe combined EtOAc layer was washed with brine
8. dry with materialdried over anhydrous Na2SO4
9. concentrationconcentrated

ORD record

ord-de2c830ba13f49369f848f08ff037fd2

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062070B2