Ethanol → Ethyl 4-fluoro-2-hydroxybenzoate

To a solution of 4-fluoro-2-hydroxybenzoic acid (3.0 g) in ethanol (40 mL) was added thionyl chloride (5.61 mL) at 0° C., and this mixture was heated to reflux for 24 hours. This reaction mixture was concentrated, and this residue was poured into water, and this mixture was extracted with ethyl acetate. This organic layer was washed with water and brine, dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 4-fluoro-2-hydroxybenzoic acid ethyl ester (3.5 g). To a solution of 4-fluoro-2-hydroxybenzoic acid ethyl ester (3.5 g) in dichloromethane (30 mL) were added N,N-diisopropylethylamine (5.0 g) and (chloromethyl)methyl ether (2.3 g) at 0° C., and this reaction mixture was stirred at room temperature overnight. This reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. This organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane) to give the title compound (2.8 g).

1. temperaturethis mixture was heated
2. temperatureto reflux for 24 hours
3. concentrationThis reaction mixture was concentrated
4. additionthis residue was poured into water
5. extractionthis mixture was extracted with ethyl acetate
6. washThis organic layer was washed with water and brine
7. dry with materialdried over anhydrous magnesium sulfate
8. customThe solvent was removed under reduced pressure

ORD record

ord-ba38858e70fc4d1eb5bc434507e7dfc8

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08227500B2