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

HRID 1049504
Notes
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Reaction equation

HRID 1049504 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 53487920Ethyl 2-bromo-5-hydroxybenzoate

Product 1

HCID 117759944Ethyl 2'-fluoro-4-hydroxy-5'-methoxy-[1,1'-biphenyl]-2-carboxylateYield 103.1%

Reagents, catalysts & solvents

4
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent

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

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes