Diisopropylamine → 1-(5-Bromo-2-fluorophenyl)-2,2,2-trifluoroethan-1-one

Temperature

-40 °C

Diisopropylamine (4.40 mL, 31.4 mmol) was dissolved in THF (28 mL) and cooled to −40° C. Then n-butyllithium (12.6 mL, 2.5 M in hexanes, 31.4 mmol) was added dropwise, and the reaction was stirred at −40° C. for 1 h, then cooled to −78° C. A solution of 1-bromo-4-fluorobenzene (5 g, 28.6 mmol) in THF (6.0 mL) was added, and the reaction was stirred at −78° C. for 1 h. Trifluoroacetic acid ethyl ester (3.73 mL, 31.4 mmol) in THF (6.0 mL) was then added, and the reaction was slowly warmed to 0° C. over an hour. The reaction was quenched with NH4Cl (aq. sat), and extracted with EtOAc, washed with brine, and dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtOAc/heptane) provided 1-(5-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone.

1. temperaturecooled to −78° C
2. stirringthe reaction was stirred at −78° C. for 1 h
3. temperaturethe reaction was slowly warmed to 0° C. over an hour
4. customThe reaction was quenched with NH4Cl (aq. sat)
5. extractionextracted with EtOAc
6. washwashed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification by normal phase silica gel column chromatography (EtOAc/heptane)

ORD record

ord-5d4e47f26ab7458387dde43b0a3f06f5

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09199994B2