Methanol → 4-Bromo-2-fluoro-benzoic acid methyl ester

Temperature

25 °C

To a 500-mL three neck round-bottom flask was added a solution of 4-bromo-2-fluorobenzoic acid (30.0 g, 137 mmol, 1.00 equiv) in methanol (200 mL). SOCl2 (24.0 g, 202 mmol, 1.50 equiv) was added dropwise at 0° C. The resulting solution was stirred for 10 min at 0° C., for 30 min at 25° C., and then for 3 h at 50° C. After cooling to room temperature, the resulting mixture was concentrated under reduced pressure. The residue was partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous phase was extracted with 100 mL of ethyl acetate. The combined organic layers were washed with 1×100 mL of water, 1×100 mL of sodium bicarbonate (aq. sat.) and 1×100 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield 30.0 g (94%) of the title compound as a light yellow solid.

1. waitfor 3 h at 50° C
2. temperatureAfter cooling to room temperature
3. concentrationthe resulting mixture was concentrated under reduced pressure
4. customThe residue was partitioned between water (100 mL) and ethyl acetate (100 mL)
5. extractionThe aqueous phase was extracted with 100 mL of ethyl acetate
6. washThe combined organic layers were washed with 1×100 mL of water, 1×100 mL of sodium bicarbonate (aq. sat.) and 1×100 mL of brine
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure

ORD record

ord-ee7ec73d805a432ea3beb0e9bc4681b4

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2