Sodium hydride → Benzoic acid, 3-bromo-4-(2,2,2-trifluoroethoxy)-, methyl ester

Temperature

0 °C

Sodium hydride (60% dispersion in mineral oil, 520 mg, 13.0 mmol) was added to a stirred, cooled (0° C.) solution of methyl 3-bromo-4-hydroxybenzoate (Description 64, 3.0 g, 13.0 mmol) in N,N'-dimethylformamide (100 ml) and the mixture was stirred at 0° C. for 15 min. 2,2,2-Trifluoroethyltosylate (6.61 g, 26.0 mmol) in N,N'-dimethylformamide (50 ml) was added and the mixture was stirred at 100° C. for 16 h. The mixture was concentrated under reduced pressure to half volume and poured into aqueous sodium hydroxide solution (1 M, 300 ml). The mixture was extracted with ethyl acetate (2×350 ml) and the combined organic fractions were dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc to give the title compound as a colorless oil (1.37 g, 34%). 1H NMR (250 MHz, CDCl3) δ8.27 (1 H, d, J 2.1 Hz), 7.99 (1 H, dd, J 2.1, 8.6 Hz), 6.92 (1 H, d, J 8.6 Hz), 4.42-4.52 (2 H, quartet, J 7.9 Hz), and 3.91 (3 H, s).

1. stirringthe mixture was stirred at 100° C. for 16 h
2. concentrationThe mixture was concentrated under reduced pressure to half volume
3. additionpoured into aqueous sodium hydroxide solution (1 M, 300 ml)
4. extractionThe mixture was extracted with ethyl acetate (2×350 ml)
5. dry with materialthe combined organic fractions were dried (Na2SO4)
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by column chromatography on silica gel
8. washeluting with hexane/EtOAc

ORD record

ord-8ec49a3dcae74e97bd2a54ba624c9dec

Source dataset

uspto-grants-2000_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06071927