Dimethylformamide → 5-(3-Fluorophenyl)-2-methylbenzoic acid

HRID 1771595Notes

Reaction equation

HRID 1771595 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>CCO.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.O>[F:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=2)[C:7]([OH:9])=[O:8])[CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 3460045-Bromo-2-methylbenzoic acidHCID 27339863-Fluorophenylboronic acid

Product 1

HCID 463145835-(3-Fluorophenyl)-2-methylbenzoic acidYield 72.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-2-methyl-benzoic acid (1 g, 5.12 mmol, 1.0 eq) and (3-fluorophenyl)boronic acid (720 mg, 4.65 mmol, 1.1 eq) in a mixture of EtOH (5 mL), DMF (20 mL) and H2O (5 mL) were added Na2CO3 (1.98 g, 18.68 mmol, 4 eq) and Pd(PPh3)4 (270 mg, 0.23 mmol, 0.05 eq). The mixture was heated at 100° C. under N2 for 4 h and the reaction quenched by addition of 1M HCl. The aqueous phase was extracted with EtOAc and the combined organic extracts washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by chromatography (petroleum ether:EtOAc, 20:1 to 1:1) to give the title compound as a white solid (780 mg, 68%).

Workup

  1. customthe reaction quenched by addition of 1M HCl
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washthe combined organic extracts washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by chromatography (petroleum ether:EtOAc, 20:1 to 1:1)

Sources & evidence

ORD record
ord-070138bfe0b0466eb9da73522112c407
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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