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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence