Sodium Carbonate → Ethyl 2'-fluoro-4-hydroxy-5'-methoxy-[1,1'-biphenyl]-2-carboxylate

HRID 1049504Notes

Reaction equation

Br[C:2]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[F:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[C:2]1[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Under an argon atmosphere, to a solution of ethyl 2-bromo-5-hydroxybenzoate (1.13 g) in toluene (30 mL) were added 2-fluoro-5-methoxyphenylboronic acid (1.18 g), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (379 mg), 75% tris(dibenzylideneacetone)dipalladium (0) (281 mg) and 2.0 M aqueous sodium carbonate solution (6.9 mL), and the mixture was stirred at 100° C. for 21.5 hr. The reaction mixture was diluted with water and 1N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.38 g) as a pale-yellow oil.

Workup

extractionextracted with ethyl acetate
washThe extract was washed with saturated brine
dry with materialdried over anhydrous sodium sulfate
customThe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record: ord-ee6a8bd2a1ee4ebf87d9057fc08928d9
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382188B2

Reaction notes

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