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

HRID 567873

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 solution was partitioned between ethyl acetate and dilute hydrochloric acid, and the organic phase was washed in water and in an aqueous 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 2H-NMR (90 MHz, CDCl3), the compound has the peaks shown below.

Workup

customThe resulting solution was partitioned between ethyl acetate and dilute hydrochloric acid
washthe organic phase was washed in water and in an aqueous 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-efbdaef15b4a47079767403f833f42af
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06180659B2

Linked notes

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