Sulfuric Acid → (5-Bromo-4-fluoro-2-methyl-phenyl)-acetic acid methyl ester

HRID 1962373Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9](Cl)(Cl)Cl)[C:5]([CH3:13])=[CH:4][C:3]=1[F:14].[CH3:15][O-:16].[Na+].S(=O)(=O)(O)[OH:19]>CO>[CH3:15][O:16][C:9](=[O:19])[CH2:8][C:6]1[CH:7]=[C:2]([Br:1])[C:3]([F:14])=[CH:4][C:5]=1[CH3:13]

Participants

Conditions

Temperature: 5 °C

Procedure

To a solution of 1-bromo-2-fluoro-4-methyl-5-(2,2,2-trichloro-ethyl)-benzene (29.2 g) in methanol (100 ml) was added a sodium methoxide solution (30% in methanol, 78.2 ml) dropwise. The reaction mixture was stirred at reflux for 24 hours, cooled to 5° C. and treated with concentrated sulfuric acid (13.2 ml) dropwise. After further warming to reflux for 21 hours, the mixture was concentrated and the residue diluted with water/ethyl acetate. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate/cyclohexane 1:3). Yield: 18.76 g of (5-bromo-4-fluoro-2-methyl-phenyl)-acetic acid methyl ester as an oil.

Workup

temperatureat reflux for 24 hours
temperatureAfter further warming
temperatureto reflux for 21 hours
concentrationthe mixture was concentrated
additionthe residue diluted with water/ethyl acetate
extractionThe aqueous layer was extracted with ethyl acetate
washthe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue was purified by chromatography on silica gel (ethyl acetate/cyclohexane 1:3)

Sources & evidence

ORD record: ord-62db5efd29ae48b7a130db8f1ca5b702
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415369B2

Reaction notes

Loading…