Diisopropylamine → 2',4'-Difluoro-5-(1-hydroxy-1-methylethyl)biphenyl-3-carboxylic acid

HRID 888403Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([OH:14])([CH3:13])[CH3:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1B(O)O.C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+].C(NC(C)C)(C)C>CN(C)C=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[C:2]1[CH:10]=[C:9]([C:11]([OH:14])([CH3:13])[CH3:12])[CH:8]=[C:4]([C:5]([OH:7])=[O:6])[CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3-bromo-5-(1-hydroxy-1-methylethyl)benzoic acid (150 mg, 0.579 mmol) in N,N-dimethylformamide (2.90 mL) and water (0.97 mL) was added (2,4-difluorophenyl)boronic acid (110 mg, 0.695 mmol), palladium(II) acetate (6.5 mg, 0.029 mmol), 3,3′3″-phosphinidynetris(benzenesulfonic acid)trisodium salt (49.4 mg, 0.087 mmol) and diisopropylamine (0.206 mL, 1.45 mmol) and the mixture was heated to 80° C. After 3 h, filtration and purification by reverse phase chromatography (C-18, 90% water/acetonitrile→30% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (156 mg).

Workup

filtrationfiltration and purification by reverse phase chromatography (C-18, 90% water/acetonitrile→30% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-5122ab25e966489aa970d3c88e12bf0e
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08247401B2

Reaction notes

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