p-Toluenesulfonic acid → p-Methoxyphenylpropionic acid

HRID 2291149Notes

Reaction equation

HRID 2291149 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH:10](Br)C)=[CH:5][CH:4]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+].[C:28]([O-:31])(=[O:30])C.[K+].[OH-].[K+]>O.C(O)CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH3:10])[C:28]([OH:31])=[O:30])=[CH:7][CH:8]=1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 14797Potassium HydroxideHCID 2991022-bromo-1-(4-methoxyphenyl)propan-1-oneHCID 517044Potassium AcetateHCID 10942334Sodium Methoxide

Product 1

HCID 257576p-Methoxyphenylpropionic acidYield 38%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 1-(4'-methoxyphenyl)-2-bromo-1-propanone (24,3 g; 0.1 mole), p-toluenesulphonic acid (1,9 g; 0,01 mole) and ethylene glycol (750 ml) is heated at 115° C. under vacuum (40 mmHg) for three hours, while distilling off a mixture of glycol and water. To the mixture cooled to 60° C., neutralized by means of sodium methoxide (0.6 g; 0.011 mole), potassium acetate (11,77 g; 0,12 mole) is added, and the mixture is heated at 130° C. for 6 hours. The mixture is then cooled to 90° C., to it 40%-concentrated potassium hydroxide (30 ml) is added, and the mixture is kept at the temperature said for 5 hours. After cooling to room temperature, the reaction mixture is poured into water (200 ml) and extracted with methylene chloride (2×250 ml). The aqueous phase is then made acid by means of concentrated hydrochloric acid, and extracted with methylene chloride (4×250 ml). The methylene chloride phase is washed with water (4×500 ml), separated and evaporated under vacuum. The residual oil is dissolved in a 10% solution of sodium bicarbonate (500 g), treated with charcoal (1 g) and filtered on celite. The so-obtained clear solution is cooled to 0° C. and made acid to pH 1 by means of concentrated HCl. 2-(4'-Methoxyphenyl)-propionic acid precipitates (7 g; 0,038 mole). Yield of 38%; melting point 54°-55° C.

Workup

  1. distillationwhile distilling off
  2. additiona mixture of glycol and water
  3. temperatureTo the mixture cooled to 60° C.
  4. additionis added
  5. temperaturethe mixture is heated at 130° C. for 6 hours
  6. additionis added
  7. temperatureAfter cooling to room temperature
  8. extractionextracted with methylene chloride (2×250 ml)
  9. extractionextracted with methylene chloride (4×250 ml)
  10. washThe methylene chloride phase is washed with water (4×500 ml)
  11. customseparated
  12. customevaporated under vacuum
  13. dissolutionThe residual oil is dissolved in a 10% solution of sodium bicarbonate (500 g)
  14. additiontreated with charcoal (1 g)
  15. filtrationfiltered on celite
  16. temperatureThe so-obtained clear solution is cooled to 0° C.
  17. custom2-(4'-Methoxyphenyl)-propionic acid precipitates (7 g; 0,038 mole)

Sources & evidence

ORD record
ord-2e4cafa69fcf47f891c4974d34f47244
Source dataset
uspto-grants-1986_10
Patent number
US04620031

Reaction notes

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