4-Hydroxyphthalic acid → 4-(4-Fluoro-benzyloxy)-phthalic acid

HRID 1070680Notes

Reaction equation

HRID 1070680 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:11]([OH:13])=[O:12])[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=[O:7].[OH-].[K+].[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1>O>[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][O:1][C:2]2[CH:3]=[C:4]([C:11]([OH:13])=[O:12])[C:5](=[CH:9][CH:10]=2)[C:6]([OH:8])=[O:7])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 118814-Hydroxyphthalic acidHCID 14797Potassium HydroxideHCID 680214-Fluorobenzyl bromide

Product 1

HCID 223970954-(4-Fluoro-benzyloxy)-phthalic acidYield 29.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-hydroxyphthalic acid (5.0 g, 27 mmol), potassium hydroxide (5.4 g, 30 mmol) and 4-fluorobenzylbromide (5.7 g, 30 mmol) in water (13 mL) was heated under reflux for 5 h. After cooling to room temperature, the mixture was washed with ether. The aqueous phase was then acidified to pH 2 at 0° C. with concentrated HCl and then extracted with ethyl acetate. The organic extracts were then washed with water and dried over sodium sulfate. Filtration and evaporation gave a residue which was purified by chromatography (SiO2, CHCl3:Acetone:AcOH:90:9:1) to afford the title compound (2.3 g, 29%) as a colorless oil. MS: m/e=289.0 (M−H+).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 5 h
  3. washthe mixture was washed with ether
  4. customwas then acidified to pH 2 at 0° C. with concentrated HCl
  5. extractionextracted with ethyl acetate
  6. washThe organic extracts were then washed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationFiltration and evaporation
  9. customgave a residue which
  10. customwas purified by chromatography (SiO2, CHCl3:Acetone:AcOH:90:9:1)

Sources & evidence

ORD record
ord-acd00f9168fc4852814336d0c32e0211
Source dataset
uspto-grants-2005_06
Patent number
US06903095B2

Reaction notes

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