Hydrochloric Acid → Bis(3-(trifluoromethoxy)phenyl)methanone

Temperature

-78 °C

To a solution of 1-bromo-3-(trifluoromethoxy)benzene (1.52 g, 6.3 mmol) in diethyl ether (50 mL) at −78° C. was added dropwise a solution of 1.6 M n-BuLi in hexane (4.2 mL, 6.6 mmol) and the reaction mixture was stirred at −78° C. for 30 min. A solution of 3-(trifluoromethoxy)benzonitrile (1.23 g, 6.6 mmol) in diethyl ether (5 mL) was added dropwise and the reaction mixture was stirred at −78° C. for 1.5 h. 3N HCl (40 mL) was added and the reaction was allowed to warm to rt followed by stirring at rt for 1.5 h. The reaction mixture was diluted with H2O (40 mL) and extracted with EtOAc (3×75 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to yield a residue. The residue was purified by a silica gel ISCO cartridge with elution at gradient 10% EtOAc/hexane to give bis(3-(trifluoromethoxy)phenyl)methanone (1.99 g, 90% yield) as a white solid. LCMS: RT=2.10 min [M+H] 351.3 (2 min Phenomenex Luna C18 column, 4.6 X 30 mm eluting with 10-90% MeOH/H20 over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz IH (CDC13) ppm 7.46 (d, J=8.35 Hz 1 H), 7.54 (t, J=7.91 Hz, 1 H), 7.64 (s, 1 H), 7.70 (d, J=7.91 Hz, 1 H).

1. stirringthe reaction mixture was stirred at −78° C. for 1.5 h
2. temperatureto warm to rt
3. stirringby stirring at rt for 1.5 h
4. extractionextracted with EtOAc (3×75 mL)
5. dry with materialThe combined organic extracts were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto yield a residue
9. customThe residue was purified by a silica gel ISCO cartridge with elution at gradient 10% EtOAc/hexane

ORD record

ord-7d47cb12c35749b3bebd98791aaa6b36

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404896B2