3,5-Dimethoxyphenol → 2-(3,5-Dimethoxyphenoxy)-6-fluorophenyl acetic acid

HRID 3687

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][C:10]([OH:12])=[O:11].[CH3:13][O:14][C:15]1[CH:16]=[C:17]([OH:23])[CH:18]=[C:19]([O:21][CH3:22])[CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu](I)I.[Cu].CN(C)C=O>[CH3:22][O:21][C:19]1[CH:18]=[C:17]([CH:16]=[C:15]([O:14][CH3:13])[CH:20]=1)[O:23][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][C:10]([OH:12])=[O:11]

Participants

Conditions

Temperature: 120 °C

Procedure

N,N-Dimethylformamide (20 ml) was added to 2-chloro-6-fluorophenyl acetic acid (3.77 g), 3,5-dimethoxyphenol (3.08 g), potassium carbonate (5.52 g), copper iodide (950 mg) and copper (250 mg), for stirring at 120° C. for 20 hours. The resulting reaction solution was partitioned with ethyl acetate and dilute hydrochloric acid, and the organic phase was washed in water and in a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate, to distill off the solvents under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=7:3), to recover 2-(3,5-dimethoxyphenoxy)-6-fluorophenyl acetic acid (5.27 g; yield of 86%). By 1H-NMR (90 MHz, CDCl3), the compound has the peaks shown below.

Workup

customThe resulting reaction solution
customwas partitioned with ethyl acetate and dilute hydrochloric acid
washthe organic phase was washed in water and in a saturated sodium chloride solution
dry with materialdried over anhydrous magnesium sulfate
distillationto distill off the solvents under reduced pressure
customThe residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=7:3)

Sources & evidence

ORD record: ord-83441b5019214471922280f5515c2e22
Source dataset: uspto-grants-1998_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05734067

Linked notes

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