4-Bromo-2-fluorobenzoic acid → tert-Butyl 4-bromo-2-fluorobenzoate

A slurry of 4-bromo-2-fluorobenzoic acid (20.16 g, 92 mmol) in dioxane (90 mL) and conc. H2SO4 (5 mL) was cooled to 0° C., and then bubbled through with isobutene for 2 h. The reaction was allowed to gradually warm up to room temperature overnight. Solid NaHCO3 (40 g) was carefully added to the reaction and the mixture was stirred for 1 h. The mixture was concentrated, and then redissolved in water and ethyl acetate. The layers were separated. The aqueous phase was washed with ethyl acetate. The combined organics were washed with sat aq NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated. The resulting oily tert-butyl 4-bromo-2-fluorobenzoate was used without further purification. 1H NMR (400 MHz, MeOH-d4) δ ppm 7.79-7.70 (m, 1H), 7.42-7.23 (m, 3H), 1.59 (s, 11H).

1. custombubbled through with isobutene for 2 h
2. additionSolid NaHCO3 (40 g) was carefully added to the reaction
3. concentrationThe mixture was concentrated
4. dissolutionredissolved in water
5. customThe layers were separated
6. washThe aqueous phase was washed with ethyl acetate
7. washThe combined organics were washed with sat aq NaHCO3 and brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe resulting oily tert-butyl 4-bromo-2-fluorobenzoate was used without further purification

ORD record

ord-ba05d522df4a4b11b5eb0c85cbec0e44

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242996B2