Hydrochloric Acid → 3-{[4-(5-Fluoro-1-benzofuran-7-yl)phenoxy]methyl}benzoic acid

HRID 928650Notes

Reaction equation

HRID 928650 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.Br[CH2:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=1)[C:23]([O:25]C)=[O:24].C(=O)([O-])[O-].[K+].[K+].[OH-].[Li+].Cl>C1COCC1.CO.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:19][C:20]3[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=3)[C:23]([OH:25])=[O:24])=[CH:13][CH:12]=2)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 517981Methyl 3-(bromomethyl)benzoateHCID 90384207HCID 90384207, compound

Product 1

HCID 903843213-{[4-(5-Fluoro-1-benzofuran-7-yl)phenoxy]methyl}benzoic acidYield 94%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the compound (170 mg, 0.745 mmol) of Step 2, methyl 3-(bromomethyl)benzoate (256 mg, 1.12 mmol), and potassium carbonate (206 mg, 1.49 mmol), DMF (4 mL) was added, and stirred overnight. The solvent was distilled away under reduced pressure, and after diluted with ethyl acetate, the resultant was washed with the water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane/ethyl acetate). To the resulting compound (267 mg, 0.709 mmol), methanol (5 mL) and THF (5 mL) were added. A 1 N lithium hydroxide aqueous solution (1.5 mL) was added thereto under ice-cooling, and stirred at room temperature overnight. After a 1N hydrochloric acid aqueous solution (2 mL) were added thereto under ice-cooling, the solid obtained by concentrating the solvent was collected by filtration to thus obtain the title compound.

Workup

  1. distillationThe solvent was distilled away under reduced pressure
  2. additionafter diluted with ethyl acetate
  3. washthe resultant was washed with the water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled away under reduced pressure
  6. customThe resulting residue was purified by silica gel chromatography (hexane/ethyl acetate)
  7. temperatureunder ice-cooling
  8. stirringstirred at room temperature overnight
  9. temperatureunder ice-cooling
  10. customthe solid obtained
  11. concentrationby concentrating the solvent
  12. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-18e28a928bdf42fd95870a9f37e562fb
Source dataset
uspto-grants-2016_03
Patent number
US09290487B2

Reaction notes

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