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

HRID 2040930Notes

Reaction equation

HRID 2040930 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][C:17]([O:19]C)=[O:18].C(=O)([O-])[O-].[Cs+].[Cs+].NCC(O)=O>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([OH:19])=[O:18])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 750GlycineHCID 46844-ChlorophenolHCID 10796Cesium carbonateHCID 8063364Methyl 2-(2-bromophenyl)acetate

Product 1

HCID 122458712-(2-(4-Chlorophenoxy)phenyl)acetic acidYield 76.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
48 °C

Procedure

27.8 g (216 mmol) of 4-chlorophenol and 47 g (205 mmol) of methyl 2-bromophenylacetate were suspended in 790 mL of dioxane. The mixture was heated to 48° C. and 141 g of cesium carbonate, 4.5 g of glycine and 8.6 g of cuprous chloride were added. The resulting suspension was heated to reflux and stirred at this temperature for 5 days. After cooling down to room temperature, the solid was removed by filtration, washed with 100 mL of dioxane, and discarded. The mother liquors were combined and concentrated under vacuum. 100 mL of ethyl acetate were added to the residue, and the pH was adjusted to 1 with HCl 2 M. The organic phase was extracted, washed with brine and dried. The solvent was removed under vacuum. 100 mL of water were added to the residue, and the pH was adjusted to 1 with HCl 2 M. The resulting suspension was stirred and filtered, to obtain 41 g of 2-(4-chlorophenoxy)phenylacetic acid (compound XIVb) as a brown solid. Yield: 76.1%.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux
  3. temperatureAfter cooling down to room temperature
  4. customthe solid was removed by filtration
  5. washwashed with 100 mL of dioxane
  6. concentrationconcentrated under vacuum
  7. addition100 mL of ethyl acetate were added to the residue
  8. extractionThe organic phase was extracted
  9. washwashed with brine
  10. customdried
  11. customThe solvent was removed under vacuum
  12. addition100 mL of water were added to the residue
  13. stirringThe resulting suspension was stirred
  14. filtrationfiltered

Sources & evidence

ORD record
ord-2e6c31fd9e2c472a9507d14f17e47ae6
Source dataset
uspto-grants-2013_11
Patent number
US08580972B2

Reaction notes

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