4-Methoxyphenol → 1-Methoxy-4-(4-methylphenoxy)benzene

HRID 1909650Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.I[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O>[Cu](I)I.O1CCOCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 90 °C

Procedure

4-methoxy phenol (18 g, 0.145 mol) was taken into anhydrous dioxane (250 mL). 4-iodotoluene (47.42 g, 0.217 mol), cesium carbonate (94.49 g, 0.29 mol), N,N-dimethylglycine HCl (1.97 g, 0.014 mol), and copper iodide (0.966 g, 0.005 mol) were added to the solution. The reaction was heated to 90° C. for 12 h under nitrogen, with mechanical stirring. The reaction was concentrated to dryness and the residue was partitioned between water and ethyl acetate. The aqueous layer was washed with ethyl acetate (4×). The ethyl acetate was washed with brine, dried over sodium sulfate and concentrated to dryness. The crude product was purified by flash chromatography (10:1 silica ratio, eluted with 3% ethyl acetate in hexane) to obtain the title product (23.50 g, 0.1097 moles, 76% yield). 1H NMR (400 MHz, DMSO-d6); δ 2.26 (s, 3H), 3.73 (s, 3H), 6.82 (d, J=8.8, 2H), 6.94 (s, 4H), 7.14 (d, J 8, 2H).

Workup

concentrationThe reaction was concentrated to dryness
customthe residue was partitioned between water and ethyl acetate
washThe aqueous layer was washed with ethyl acetate (4×)
washThe ethyl acetate was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated to dryness
customThe crude product was purified by flash chromatography (10:1 silica ratio, eluted with 3% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-5a865f3a4d9f4de1856ae459c6d31943
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598359B2

Reaction notes

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