Carbon Dioxide → HCID 86685086, compound

Temperature

-78 °C

To a solution of 4-bromo-2-fluoro-1-methylbenzene (21.9 g, 116 mmol) in THF (100 mL) was added lithium diisopropylamide (LDA) (2 M solution in THF, 69 mL, 139 mmol) at −78° C. After being stirred at −78° C. for 1 h, the reaction was treated with excess solid carbon dioxide, and stirred while the reaction temperature slowly rose to room temperature. The mixture was concentrated and then partitioned between 4N NaOH and ethyl acetate. The aqueous phase was adjusted to pH 2 with 2N HCl and then extracted three times with ethyl acetate. The combined extracts were washed with water and brine, dried over with anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluted with EA to give methyl 6-bromo-2-fluoro-3-methylbenzoic acid (23.3 g, 86.2%) as a white solid.

1. stirringstirred while the reaction temperature
2. customslowly rose to room temperature
3. concentrationThe mixture was concentrated
4. custompartitioned between 4N NaOH and ethyl acetate
5. extractionextracted three times with ethyl acetate
6. washThe combined extracts were washed with water and brine
7. dry with materialdried over with anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by column chromatography on silica gel
11. washeluted with EA

ORD record

ord-0da151b2ac08483bb42be1c9abb25b06

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156860B2