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

HRID 1022385Notes

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) is added a sodium methoxide solution (30% in methanol, 78.2 ml) dropwise. The reaction mixture is 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 is concentrated and the residue diluted with water/ethyl acetate. The aqueous layer is extracted with ethyl acetate, the combined organic layers are washed with brine, dried over sodium sulfate and concentrated. The residue is 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 is concentrated
additionthe residue diluted with water/ethyl acetate
extractionThe aqueous layer is extracted with ethyl acetate
washthe combined organic layers are washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue is purified by chromatography on silica gel (ethyl acetate/cyclohexane 1:3)

Sources & evidence

ORD record: ord-6381524a03d04d08a6ce5d06a44d1b80
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722578B2

Reaction notes

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