Methanol → Methyl 3-chloro-4-hydroxyphenylacetate

HRID 2076622Notes

Reaction equation

HRID 2076622 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:8]=[C:9]([CH2:14][C:15]([OH:17])=[O:16])[CH:10]=[CH:11][C:12]=1[OH:13].[CH3:18]O>>[Cl:6][C:7]1[CH:8]=[C:9]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:10]=[CH:11][C:12]=1[OH:13]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 1185343-Chloro-4-hydroxyphenylacetic acid

Product 1

HCID 92625Methyl 3-chloro-4-hydroxyphenylacetate

Procedure

Sulfuric acid (1 ml) was added dropwise to a solution of 3-chloro-4-hydroxyphenylacetic acid (3.7 g, 20 mmol) in methanol at 0° C. The temperature of the reaction mixture was returned to room temperature and the mixture was stirred for 4 hours. After the solvent was removed under reduced pressure, the residue was poured into water and extracted with ethyl acetate. The organic layer was successively washed with water, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was subjected to silica gel column chromatography (eluting solvent: ethyl acetate) to obtain give crude methyl (3-chloro-4-hydroxyphenyl)acetate. Pyridine (8 ml, 99 mmol) and trifluoromethanesulfonic anhydride (3.4 ml, 20 mmol) were added dropwise to a solution of the crude compound obtained in the above in methylene chloride (30 ml) under ice-cooling, and the mixture was stirred for 1 hour. The reaction mixture was poured into a 1N aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was successively washed with water, diluted hydrochloric acid and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=3/1) to give methyl (3-chloro-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)acetate as a colorless solid (6.3 g, yield: 95%).

Workup

  1. customwas returned to room temperature
  2. customAfter the solvent was removed under reduced pressure
  3. additionthe residue was poured into water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was successively washed with water
  6. dry with materiala saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
  7. customThe residue obtained
  8. customby removing the solvent under reduced pressure
  9. washwas subjected to silica gel column chromatography (eluting solvent: ethyl acetate)
  10. customto obtain

Sources & evidence

ORD record
ord-9a9a52d141704db88c0f99530f415aec
Source dataset
uspto-grants-2011_04
Patent number
US07923573B2

Reaction notes

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