2,2,2-Trifluoroethanol → 5-Formyl-2-[(2,2,2-trifluoroethyl)oxy]benzonitrile

A solution of 2,2,2-trifluoroethanol (0.098 ml, 1.341 mmol) in DMF (9 ml) was cooled in an ice bath. Sodium hydride (60%; 38.6 mg, 0.965 mmol) was added and the resulting mixture was stirred for 10 mins before adding 2-fluoro-5-formylbenzonitrile (Aldrich; 200 mg, 1.341 mmol). The ice bath was removed and the reaction mixture was stirred at room temperature overnight. The mixture was partitioned between ethyl acetate (15 ml) and brine (7 ml). The organic layer was washed with water (2×8 ml) and brine (7 ml), passed through a phase separation cartridge and concentrated under vacuum. The residue was purified by column chromatography on silica, eluting with 0-40% ethyl acetate in cyclohexane gave the title compound as a white solid (155 mg).

1. customThe ice bath was removed
2. stirringthe reaction mixture was stirred at room temperature overnight
3. customThe mixture was partitioned between ethyl acetate (15 ml) and brine (7 ml)
4. washThe organic layer was washed with water (2×8 ml) and brine (7 ml)
5. custompassed through a phase separation cartridge
6. concentrationconcentrated under vacuum
7. customThe residue was purified by column chromatography on silica
8. washeluting with 0-40% ethyl acetate in cyclohexane

ORD record

ord-70aac211845947788b1bd7e1b5443487

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329730B2