Potassium Hydroxide → 3-Bromo-4-(methoxycarbonyl)benzoic acid

Temperature

25 °C

Potassium hydroxide (2.87 g, 51 mmol) was added to a solution of 2-bromo-1,4-benzenedicarboxylic acid, dimethyl ester (14 g, 51 mmol) in methanol (50 mL) at 25° C. The reaction mixture was stirred at 25° C. for 24 h and then at 50° C. for 3 h. The solvent was concentrated under reduced pressure and the residue was diluted with water (100 mL) and extracted with ethyl acetate (2×200 mL). The water layer was acidified to pH 2 with 2N hydrochloric acid solution and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting solid was boiled in toluene (100 mL) and the insolubles were removed by filtration. The filtrate was concentrated to dryness under reduced pressure and the resulting solid was flash chromatographed (silica gel, 50% ethyl acetate in petroleum ether with 1% acetic acid) to give 3-bromo-4-(methoxycarbonyl)benzoic acid (3.28 g, 24% yield) as a colorless solid.

1. waitat 50° C. for 3 h
2. concentrationThe solvent was concentrated under reduced pressure
3. additionthe residue was diluted with water (100 mL)
4. extractionextracted with ethyl acetate (2×200 mL)
5. extractionextracted with ethyl acetate (2×200 mL)
6. washThe combined organic layers were washed with brine (100 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customthe insolubles were removed by filtration
11. concentrationThe filtrate was concentrated to dryness under reduced pressure
12. customchromatographed (silica gel, 50% ethyl acetate in petroleum ether with 1% acetic acid)

ORD record

ord-99a0166247e547c1889ff6e93cf759c0

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515124B2