Hydrochloric Acid → 2-Fluoro-3-(3-fluorophenyl)-5-methoxybenzoic acid

HRID 1771611Notes

Reaction equation

HRID 1771611 reaction equation
[F:1][C:2]1[C:10](I)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].Cl>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C.CCO>[F:1][C:2]1[C:10]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([F:14])[CH:20]=2)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 894441282-Fluoro-3-iodo-5-methoxybenzoic acid

Product 1

HCID 894438332-Fluoro-3-(3-fluorophenyl)-5-methoxybenzoic acidYield 82.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-fluoro-3-iodo-5-methoxy-benzoic acid (3.0 g 10.14 mmol, 1.0 eq) in a mixture of water (30 mL), EtOH (30 mL) and DMF (60 mL), was added 3-fluorophenylboronic acid (1.56 g 11.15 mmol, 1.1 eq) and Na2CO3 (4.3 g, 40.56 mmol, 4.0 eq). The mixture was stirred at room temperature under N2 for 10 mins then Pd(PPh3)4 (1.17 g, 1.01 mmol, 0.1 eq) was added. The mixture was heated at 100° C. for 5 h then cooled to room temperature and acidified with 1M HCl. The aqueous layer was extracted with EtOAc and the combined extracts were washed with water, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a yellow solid (2.2 g, 81%).

Workup

  1. temperatureThe mixture was heated at 100° C. for 5 h
  2. temperaturethen cooled to room temperature
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined extracts were washed with water
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

Sources & evidence

ORD record
ord-8bf0f5eec2e0485c8c96fb2656efb925
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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