Acetic Acid → 2-(3,4-Difluoro-5-methoxyphenyl)acetic acid

HRID 453405Notes

Reaction equation

C([C:4]1[CH:5]=[C:6]([O:12][CH3:13])[C:7]([F:11])=[C:8]([F:10])[CH:9]=1)C=C.[C:14]([OH:17])(=[O:16])[CH3:15].O=[O+][O-].O=O>C(OCC)(=O)C.O>[F:10][C:8]1[CH:9]=[C:4]([CH2:15][C:14]([OH:17])=[O:16])[CH:5]=[C:6]([O:12][CH3:13])[C:7]=1[F:11]

Participants

Conditions

Temperature: 50 °C

Procedure

1.59 g of 5-allyl-1,2-difluoro-3-methoxybenzene (C2) are dissolved in 5.25 ml of ethyl acetate and 19.75 ml of glacial acetic acid and cooled to 0° C. in an ice bath. The solution is subsequently treated with ozone for 15 min (ozone generator: oxygen flow rate 40 l/h—corresponds to 5 g/h of O3). The mixture is subsequently diluted with 12 ml of water and warmed at 50° C. for a further 15 min. The reaction solution is then evaporated in vacuo, and the residue remaining is dissolved in 50 ml of tetrahydrofuran. 420 μl of H2O2 (30% solution) and 163 mg of phenylselenic acid are added. The reaction solution is subsequently heated under reflux for 2 h and, when the reaction is complete, evaporated to dryness in vacuo. The residue is purified by flash column chromatography on silica gel (solvent gradient: dichloromethane/0-40% by vol. of methanol), giving 806 mg of the title compound as a colourless oil; MS: 203.1 (MH+); TLC: Rf=0.40 (cyclohexane/ethyl acetate 9:1).

Workup

customThe reaction solution is then evaporated in vacuo
dissolutionthe residue remaining is dissolved in 50 ml of tetrahydrofuran
addition420 μl of H2O2 (30% solution) and 163 mg of phenylselenic acid are added
temperatureThe reaction solution is subsequently heated
temperatureunder reflux for 2 h
customevaporated to dryness in vacuo
customThe residue is purified by flash column chromatography on silica gel (solvent gradient: dichloromethane/0-40% by vol. of methanol)

Sources & evidence

ORD record: ord-0eb2886029a34a339a080b20349a34ae
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492440B2

Reaction notes

Loading…