Sodium Hydroxide → 2-(4-Fluorophenyl)-5-methoxybenzoic acid

HRID 377738Notes

Reaction equation

HRID 377738 reaction equation
C[O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1.[OH-].[Na+]>C(O)C>[CH3:11][O:10][C:8]1[CH:7]=[CH:6][C:5]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[C:4]([CH:9]=1)[C:3]([OH:19])=[O:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 154617365-Methoxy-[2-(4-fluorophenyl)] benzoic acid methyl ester

Product 1

HCID 154617372-(4-Fluorophenyl)-5-methoxybenzoic acidYield 86%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl-2-bromo-5-methoxybenzoate (15.1 g; 0.062 mol), 4-fluorobenzene boronic acid (9.98 g; 0.0713 mol), and tris (dibenzylideneacetone)dipalladium (0) (1.0 g) were dissolved in 100 mL dimethoxyethane (DME) and 100 mL 2N sodium carbonate and stirred at reflux overnight. The reaction mixture was cooled, the DME removed in vacuo, and the resulting oil partitioned between methylene chloride and water. The aqueous layer was extracted further with methylene chloride and the combined organic extracts dried over magnesium sulfate and concentrated in vacuo. Purification of the crude material by silica gel column chromatography (gradient elution with ethyl acetate/hexane) provided 5-methoxy-[2-(4-fluorophenyl)] benzoic acid methyl ester as a colorless oil (63%). The ester (8.6 g) was hydrolyzed in refluxing 1N sodium hydroxide (72 mL) and ethanol (250 mL). The reaction mixture was cooled and extracted with ethyl acetate. The aqueous layer was then acidified, extracted with EtOAc and the extracts concentrated to afford pure 5-methoxy-[2-(4-fluorophenyl)] benzoic acid in 86% yield. The acid (6.9 g; 0.03 mol) was dissolved in 50 mL thionyl chloride and refluxed overnight. The thionyl chloride was removed in vacuo to afford 2-fluoro-7-methoxy fluorenone quantitatively as an orange solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with ethyl acetate
  3. extractionextracted with EtOAc
  4. concentrationthe extracts concentrated

Sources & evidence

ORD record
ord-8a396658570044e899e6fb459dcbcc97
Source dataset
uspto-grants-2000_02
Patent number
US06028112

Reaction notes

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