Hydrochloric Acid → Methyl 2-(3-hydroxyphenoxy)-3-pyridinylacetate

HRID 467046Notes

Reaction equation

HRID 467046 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[O:6][C:7]1[C:12]([CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:11][CH:10]=[CH:9][N:8]=1.C(=O)([O-])[O-].[K+].[K+].Cl.C(Cl)(=O)C>Br.[Br-].C([P+](CCCC)(CCCC)CCCC)CCCCCCCCCCCCCCC.CO>[OH:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[O:6][C:7]1[C:12]([CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:11][CH:10]=[CH:9][N:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 11430Potassium CarbonateHCID 54150026Methyl 2-(3-methoxyphenoxy)-3-pyridinylacetate

Product 1

HCID 19771878Methyl 2-(3-hydroxyphenoxy)-3-pyridinylacetateYield 51.5%

Reagents, catalysts & solvents 3

HCID 84716Hexadecyltributylphosphonium bromideCatalystHCID 260Hydrogen BromideSolventHCID 887MethanolSolvent

Procedure

Methyl 2-(3-methoxyphenoxy)-3-pyridinylacetate (27.2 g) was heated at 115° C. in 47% hydrobromic acid (249 ml) containing hexadecyltributylphosphonium bromide (5.6 g). After 3 hours, the solution was cooled and potassium carbonate added until the pH of the solution was ca. 6. The reaction mixture was extracted (×5) with ethyl acetate. The organic extracts were dried, filtered and evaporated to give a pale orange solid. The solid was then treated with methanolic hydrogen chloride overnight (from methanol (500 ml) and acetyl chloride (50 ml)). The methanol was removed and the residue dissolved in water. The pH of the solution was adjusted to ca. pH6 with sodium bicarbonate and the solution extracted with ethyl acetate (×3). The combined organic extracts were dried, filtered ad evaporated. The resulting organge solid residue was re-dissolved in dichloromethane and filtered through a plug of silica (eluent ether dichloromethane). Evaporation afforded methyl 2-(3-hydroxyphenoxy)-3-pyridinylacetate as a pale yellow solid (13.28 g, 51%) which was used without further purification.

Workup

  1. temperaturethe solution was cooled
  2. extractionThe reaction mixture was extracted (×5) with ethyl acetate
  3. customThe organic extracts were dried
  4. filtrationfiltered
  5. customevaporated
  6. customto give a pale orange solid
  7. customThe methanol was removed
  8. dissolutionthe residue dissolved in water
  9. extractionthe solution extracted with ethyl acetate (×3)
  10. customThe combined organic extracts were dried
  11. filtrationfiltered ad
  12. customevaporated
  13. dissolutionThe resulting organge solid residue was re-dissolved in dichloromethane
  14. filtrationfiltered through a plug of silica (eluent ether dichloromethane)
  15. customEvaporation

Sources & evidence

ORD record
ord-9b422795dde04e03b4714c406e012c6b
Source dataset
uspto-grants-1992_10
Patent number
US05158954

Reaction notes

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