Hydrochloric Acid → HCID 67333310, compound

HRID 1970106Notes

Reaction equation

HRID 1970106 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11][CH3:12])=[O:10].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O.Cl>O1CCOCC1.[Cu]Cl.C(OCC)(=O)C>[CH3:12][O:11][C:9](=[O:10])[CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[O:20][C:17]1[CH:18]=[CH:19][C:14]([Cl:13])=[CH:15][CH:16]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 673N,N-DimethylglycineHCID 46844-ChlorophenolHCID 10796Cesium carbonateHCID 8063364Methyl 2-(2-bromophenyl)acetate

Product 1

HCID 67333310HCID 67333310, compoundYield 95.5%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Methyl 2-bromophenylacetate (47.0 grams 216.3 mmol) and 4-chloro-phenol (27.8 grams, 215.8 mmol) were dissolved in dioxane (790 ml) while warming to 50° C. To the resulting solution were added, under stirring in an inert nitrogen atmosphere, cesium carbonate (141 grams, 432.2 mmol) and copper(I) chloride (18.56 g, 86.2 mmol). Finally, N,N-dimethylglycine (4.46 grams, 43.2 mmol) was added to the green suspension. The reaction mixture was heated at 110° C. (reflux temperature) for 4 days while stirring. The reaction mixture was filtered over dicalite, which was washed with dioxane (40 ml). The dioxane was removed in vacuo to leave a brownish oil. Ethyl acetate (100 ml) was added to the oil and the pH of the resulting mixture was adjusted to 1 by addition of 1 M HCl (300 ml). The organic phase was washed with saturated brine (300 ml), dried on magnesium sulphate and then concentrated under vacuum to yield 57.2 grams (206 mmol; 95%) of [2-(4-chloro-phenoxy)-phenyl]-acetic acid methyl ester as a brown oil. The oil was dissolved in methanol (250 ml), whereupon KOH (16.2 grams; 1.4 eq) was added. The resulting solution was heated for 3 h at 60° C. The reaction mixture was cooled and the methanol (200 ml) was removed under vacuum. To the residue water (100 ml) was added and the pH was adjusted to 1 by addition of 1M HCl (25 ml). The resulting crystals were filtered off and dried in vacuum at 40° C. to yield 47.3 grams (180 mmol; 87%) of [2-(4-chloro-phenoxy)-phenyl]-acetic acid (IX).

Workup

  1. additionTo the resulting solution were added
  2. temperatureThe reaction mixture was heated at 110° C.
  3. temperature(reflux temperature) for 4 days
  4. filtrationThe reaction mixture was filtered over dicalite, which
  5. washwas washed with dioxane (40 ml)
  6. customThe dioxane was removed in vacuo
  7. customto leave a brownish oil
  8. washThe organic phase was washed with saturated brine (300 ml)
  9. customdried on magnesium sulphate
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-71780fa4946a42648ac5ebddbf3740c6
Source dataset
uspto-grants-2013_04
Patent number
US08426610B2

Reaction notes

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