Hydrochloric Acid → 3-(4-Methoxyphenoxy)benzoic acid

HRID 1709017Notes

Reaction equation

HRID 1709017 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7]CC)=[O:6].Br[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].Cl>[Cu].O>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([O:1][C:2]2[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=2)[C:5]([OH:7])=[O:6])=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 77304-BromoanisoleHCID 11430Potassium CarbonateHCID 24522Ethyl 3-hydroxybenzoate

Product 1

HCID 6185083-(4-Methoxyphenoxy)benzoic acidYield 81.5%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 962WaterSolvent

Procedure

Ethyl 3-hydroxybenzoate (34.0 grams (g), 0.205 mole) (Aldrich Chemical Company, Milwaukee, Wis.), 4-bromoanisole (26.0 milliliters (ml)), (38.8 g, 0.208 mole) (Aldrich Chemical Company), anhydrous potassium carbonate (17.8 g, 0.129 mole) and copper powder (10.0 g, 0.157 mole), (Fisher Scientific, Pittsburgh, Pa.) were heated under nitrogen to 190° C. with slow stirring. Water generated during the reaction was removed by means of a short-path distillation apparatus attached to the reaction flask. After 20 hours, the reaction mixture was allowed to cool and 20 percent aqueous sodium hydroxide (NaOH) (50 ml) was added. Ester hydrolysis was complete after 1 hour at reflux. The cooled reaction mixture was acidified with concentrated hydrogen chloride (HCl), partitioned between methylene chloride (CH2Cl2 (300 ml)) and water (50 ml), and filtered to remove copper powder. The phases were separated and the organic layer was washed with saturated sodium chloride (NaCl) (2×100 ml), dried with magnesium sulfate (MgSO4), filtered, and solvent evaporated to afford a light brown solid. The crude product was recrystallized from 60 percent aqueous acetic acid to afford 3-(4'-methoxyphenoxy)benzoic acid as off-white crystals (40.77 g, 0.167 mol) with a melting point (m.p.) of 120° C. to 125° C.

Workup

  1. customwas removed by means of a short-path distillation apparatus
  2. temperatureto cool
  3. addition20 percent aqueous sodium hydroxide (NaOH) (50 ml) was added
  4. customEster hydrolysis
  5. waitwas complete after 1 hour
  6. temperatureat reflux
  7. customThe cooled reaction mixture
  8. custompartitioned between methylene chloride (CH2Cl2 (300 ml)) and water (50 ml)
  9. filtrationfiltered
  10. customto remove copper powder
  11. customThe phases were separated
  12. washthe organic layer was washed with saturated sodium chloride (NaCl) (2×100 ml)
  13. dry with materialdried with magnesium sulfate (MgSO4)
  14. filtrationfiltered
  15. customsolvent evaporated
  16. customto afford a light brown solid
  17. customThe crude product was recrystallized from 60 percent aqueous acetic acid

Sources & evidence

ORD record
ord-129c81981f8441f8be3bc235cb445f50
Source dataset
uspto-grants-1990_08
Patent number
US04946926

Reaction notes

Loading…