Sulfuric Acid → 4-Fluoro-3-hydroxy-benzoic acid methyl ester

HRID 1531429Notes

Reaction equation

HRID 1531429 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[OH:11].[CH:12](OC)(OC)OC.OS(O)(=O)=O>CO>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:12])=[O:7])=[CH:4][C:3]=1[OH:11]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 9005Trimethyl orthoformateHCID 5936354-Fluoro-3-hydroxybenzoic acid

Product 1

HCID 120168924-Fluoro-3-hydroxy-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
47.5 °C

Procedure

4-Fluoro-3-hydroxybenzoic acid (20.0 g, 0.13 mol) was dissolved in anhydrous methanol (160 mL), mixed with trimethyl orthoformate (25 mL) followed by the addition of concentrated H2SO4 (3 mL) and the reaction was heated to 40-55° C. overnight. Half of the solvent was removed in vacuo, the remaining solution was poured into an ice/H2O mixture and the product was extracted twice with diethyl ether. The combined ether phases were washed twice with H2O, treated with a cold solution of saturated NaHCO3, treated with brine, dried with MgSO4, filtered, and the solvent was removed in vacuo to give 21.6 g (99% yield) of a white solid as the title compound (mp 93.5-94.5° C.). Mass spectrum (70 eV) m/z (relative intensity) 170 (44, M+), 139 (100), 111 (83), 83 (83), 82 (16), 81 (11), 63 (11), 57 (24).

Workup

  1. customHalf of the solvent was removed in vacuo
  2. additionthe remaining solution was poured into an ice/H2O mixture
  3. extractionthe product was extracted twice with diethyl ether
  4. washThe combined ether phases were washed twice with H2O
  5. additiontreated with a cold solution of saturated NaHCO3
  6. additiontreated with brine
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-b553a1c3e463415bbecc6689dbd44698
Source dataset
uspto-grants-2001_03
Patent number
US06197978B1

Reaction notes

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