Methanol → Methyl 4-fluorosalicylate

4-Fluorosalicylic acid (10.0 g, 64 mmol) was dissolved in methanol (300 ml), and concentrated sulfuric acid (6.3 g, 64 mmol) was added thereto. The reaction mixture was refluxed for 48 hrs. The solvent was evaporated, and the residue was neutralized with 2 N aqueous sodium hydroxide solution. Ethyl acetate was added to the mixture. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give methyl 4-fluorosalicylate (10.0 g, 92%) as white crystals. Methyl 4-fluorosalicylate (10.0 g, 58 mmol) and N,N-dimethylthiocarbamoyl chloride (9.6 g, 77 mmol) were dissolved in DMF (100 ml), and 1,4-diazabicyclo[2.2.2]octane (8.5 g, 75 mmol) was added thereto. The reaction mixture was stirred at room temperature for 7 hrs. The reaction mixture was combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated. The residue was subjected to a silica gel column chromatography. The fractions eluted with ethylacetate-hexane (1:5, v/v) were collected, concentrated and recrystallized from ethyl acetate-hexane to give the titled compound (12.1 g, 80%) as white crystals.

1. temperatureThe reaction mixture was refluxed for 48 hrs
2. customThe solvent was evaporated
3. additionEthyl acetate was added to the mixture
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was evaporated

ORD record

ord-6b1657d03b6d4dc888f507c7303db898

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07399759B2