4-Methoxyphenol → HCID 86690883, compound

HRID 1465582Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([CH3:9])[C:3]=1[C:10](=[O:12])[CH3:11].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[F:1][C:2]1[CH:7]=[C:6]([O:29][C:26]2[CH:27]=[CH:28][C:23]([O:22][CH3:21])=[CH:24][CH:25]=2)[CH:5]=[C:4]([CH3:9])[C:3]=1[C:10](=[O:12])[CH3:11]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 1-(2-fluoro-4-iodo-6-methylphenyl)ethanone (30-4, 1.1 g, 4.0 mmol), K3PO4 (1.7 g, 8.0 mmol), 4-methoxy-phenol (0.60 g, 4.8 mmol) in toluene (20 mL) was added 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (51 mg, 0.12 mmol), Pd(OAc)2 (38 mg, 0.08 mmol). The reaction was heated at 100° C. overnight under N2. The solution was cooled to room temperature and filtered through a small pad of diatomaceous earth. The cake was washed with ethyl acetate (50 mL) and combined filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to give 1-(2-fluoro-4-(4-methoxyphenoxy)-6-methylphenyl)ethanone (0.47 g, 1.7 mmol) as yellow oil in 43% yield: 1H NMR (500 MHz, CDCl3) δ 6.97 (m, 2 H), 6.90 (m, 2 H), 6.54 (s, 1 H), 6.42 (m, 1 H), 3.80 (s, 3 H), 2.50 (d, J=4.1 Hz, 3 H), 2.30 (s, 3 H). ESI-MS: m/z 275.0 (M+H)+.

Workup

temperatureThe solution was cooled to room temperature
filtrationfiltered through a small pad of diatomaceous earth
washThe cake was washed with ethyl acetate (50 mL)
concentrationwas concentrated under reduced pressure
customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record: ord-26b5e12cfb6747b09be0e0ddd2d1e512
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999983B2

Reaction notes

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