Dimethylformamide → 5-(3-Fluorophenyl)-2-methoxy-3-methyl-benzoic acid

HRID 1771695Notes

Reaction equation

HRID 1771695 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[C:14]([CH3:23])[C:15]([O:21][CH3:22])=[C:16]([CH:20]=1)[C:17]([OH:19])=[O:18].C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>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:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:13]=[C:14]([CH3:23])[C:15]([O:21][CH3:22])=[C:16]([CH:20]=2)[C:17]([OH:19])=[O:18])[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 9619195-Bromo-2-methoxy-3-methylbenzoic acidHCID 27339863-Fluorophenylboronic acid

Product 1

HCID 894437175-(3-Fluorophenyl)-2-methoxy-3-methyl-benzoic acidYield 86%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 3-fluorophenylboronic acid (0.75 g, 5.39 mmol, 1.1 eq), 5-bromo-2-methoxy-3-methyl-benzoic acid (1.2 g, 4.90 mmol, 1.0 eq) and Na2CO3 (1.56 g, 14.69 mmol, 3 eq) in a mixture of EtOH (6 mL), DMF (24 mL) and H2O (6 mL) was added Pd(PPh3)4 (300 mg, 0.26 mmol, 0.05 eq). The mixture was stirred at 100° C. overnight. Water was added, the reaction was filtered and the filtrate was extracted with EtOAc. The organic extract was discarded and the aqueous phase was acidified to pH 4-5 with 1M HCl and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to provide the title compound as a white solid (1.09 g, 86%).

Workup

  1. filtrationthe reaction was filtered
  2. extractionthe filtrate was extracted with EtOAc
  3. extractionThe organic extract
  4. extractionextracted with EtOAc
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-4f83e560718b4adc9e29f6f73db1b870
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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