4-Chlorophenol → 2-(2-(4-Chlorophenoxy)phenyl)acetic acid

HRID 2065865Notes

Reaction equation

HRID 2065865 reaction equation
C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.Cl[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][C:23]([OH:25])=[O:24].O.Cl>[Cu]Br.O.COCCOCCOC>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][C:23]([OH:25])=[O:24])=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 46844-ChlorophenolHCID 11430Potassium CarbonateHCID 17124o-Chlorophenylacetic acid2×HCID 21885828Hydrate;hydrochloride

Product 1

HCID 122458712-(2-(4-Chlorophenoxy)phenyl)acetic acidYield 176.4%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent2×HCID 8150DiglymeSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 552.0 g (4.0 mol) of potassium carbonate and 1500 mL of diglyme was kept at 0-20° C. while adding 283.1 g (2.2 mol) of 4-chlorophenol thereto and mixing, and then 5.74 g (0.04 mol) of copper(I) bromide was added. The obtained mixture was heated to 100° C., and 90.3 g (0.53 mol) of 2-chlorophenylacetic acid was added. This mixture was stirred at the same temperature for 1 hour, and then 159.4 g (0.93 mol) of 2-chlorophenylacetic acid was further added. After stirring the obtained mixture at 120-130° C. for approximately 8 hours, completion of the reaction was confirmed by high-performance liquid chromatography. The reacted mixture was cooled to near room temperature, and then approximately 700 mL of water and approximately 650 mL of 35 wt % hydrochloric acid water were added in that order. The pH of the aqueous layer was below 1. After further adding about 500 mL of water to the obtained mixture, it was extracted once with 400 mL and once with 200 mL of toluene, in that order. The obtained organic layers were combined and washed 3 times with 500 mL of water and once with 500 mL of brine, in that order. The obtained organic layer was subjected to dehydration treatment with anhydrous magnesium sulfate, and 100 mL of heptane was added dropwise to approximately 400 g of the residue obtained by partially concentrating the treated organic layer. The internal temperature of the mixture after the dropwise addition was about 70° C., and crystals precipitated in the mixture. Upon completion of the dropwise addition, the mixture was cooled to 20-25° C. and the crystals were separated off by filtration. The obtained crystals were washed with 100 mL of a heptane/toluene=1/1 mixed solvent and dried under reduced pressure to obtain 245.6 g of 2-(2-(4-chlorophenoxy)phenyl)acetic acid as a white solid. The yield was 68.8%.

Workup

  1. customwas kept at 0-20° C.
  2. additionmixing
  3. stirringAfter stirring the obtained mixture at 120-130° C. for approximately 8 hours
  4. temperatureThe reacted mixture was cooled to near room temperature
  5. extractionwas extracted once with 400 mL and once with 200 mL of toluene, in that order
  6. washwashed 3 times with 500 mL of water
  7. additionwas added dropwise to approximately 400 g of the residue
  8. customobtained
  9. concentrationby partially concentrating the treated organic layer
  10. additionThe internal temperature of the mixture after the dropwise addition
  11. customwas about 70° C.
  12. customcrystals precipitated in the mixture
  13. additionUpon completion of the dropwise addition
  14. temperaturethe mixture was cooled to 20-25° C.
  15. customthe crystals were separated off by filtration
  16. washThe obtained crystals were washed with 100 mL of a heptane/toluene=1/1 mixed solvent
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-94212cf3cf124829a4aa61cec0d0aff6
Source dataset
uspto-grants-2012_10
Patent number
US08288564B2

Reaction notes

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