4-Iodophenol → 4',5'-Difluoro-2'-methoxy-biphenyl-4-ol

HRID 547844Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5](B(O)O)=[C:4]([O:12][CH3:13])[CH:3]=1.I[C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[C:4]([O:12][CH3:13])[CH:3]=1

Participants

Conditions

Temperature: 82.5 °C

Procedure

4,5-Difluoro-2-methoxyphenyl-boronic acid (8.8 g, 46.82 mmol) and 4-iodophenol (6.86 g, 31.21 mmol) were suspended in 165 ml of DMF. H2O (40 mL) was added and the mixture was degassed with argon. Finely ground potassium carbonate (13 g, 93.63 mmol) and tetrakis(triphenylphosphine) palladium(0) (1.5 g, 1.29 mmol) were added. The reaction was stirred at 80-85° C. for 1 hr under argon and cooled. The mixture was diluted with ethyl acetate and water. The organic layer was washed with brine, dried and solvents were evaporated. The crude product was purified by flash chromatography, eluting with 0-8% ethyl acetate in hexanes to yield 4′,5′-difluoro-2′-methoxy-biphenyl-4-ol (6.58 g, 89.3%). LR-MS (ES) calculated for C13H10F2O, 236.22; found m/z 235 [M−H]−.

Workup

customthe mixture was degassed with argon
temperaturecooled
washThe organic layer was washed with brine
customdried
customsolvents were evaporated
customThe crude product was purified by flash chromatography
washeluting with 0-8% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-ca1b55e1aeb742eca7e378533e6547e1
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07939569B1

Reaction notes

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