4-Bromophenol → 2-(4-Bromophenoxy)-5-methoxybenzoic acid

Temperature

110 °C

4-Bromophenol (8.7 g, 50 mmol), Cs2CO3 (16 g, 50 mmol), CuOTf toluene complex (2:1) (0.625 mmol, 5 mol % Cu, 150 mg), ethyl acetate (0.25 ml, 2.5 mmol) were added to a solution of 2-bromo-5-methoxybenzoic acid (11.6 g, 50 mmol) in toluene (40 mL) in a sealed tube. The reaction mixture was purged with N2, and was heated to 110° C. until the aryl halide was consumed as determined by LC-MS (48 h). After cooling to RT, the mixture was filtered through a Celite plug. The Celite plug was washed with EtOAc. The mixture was acidified by 1N HCl, and extracted w/EtOAc. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. This residue was purified via column chromatography on silica gel (gradient elution with 0-10% MeOH/DCM) to afford 2-(4-bromophenoxy)-5-methoxybenzoic acid. MS m/z=324.9 [M+H]+. Calc'd for C14H11BrO4: 323.1.

1. customThe reaction mixture was purged with N2
2. customwas consumed
3. customas determined by LC-MS (48 h)
4. temperatureAfter cooling to RT
5. filtrationthe mixture was filtered through a Celite plug
6. washThe Celite plug was washed with EtOAc
7. extractionextracted w/EtOAc
8. washThe combined organic phases were washed with brine
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThis residue was purified via column chromatography on silica gel (gradient elution with 0-10% MeOH/DCM)

ORD record

ord-157bc4bd29324e05813615e940ec24e5

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962859B2