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

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (22.1 mL, 157 mmol) in 140 mL THF was stirred under argon at −68° C. while n-BuLi (57.9 mL, 2.59 M in hexane, 150 mmol) was added in a fine stream in 2 portions over 6 min. The resulting pale yellow homogeneous solution was removed from the acetone/dry ice bath and stirred at ambient conditions for 9 min, and was then cooled back down to −68° C. and a solution of 1-bromo-4-fluorobenzene (15.6 mL, 143 mmol) in THF (30 mL) was added rapidly dropwise over 5 min. The reaction was then stirred in the cold bath for another 6 min, and the pale yellow reaction was then treated rapidly dropwise with a solution of ethyl trifluoroacetate (18.7 mL, 157 mmol) in THF (30 mL) over ˜8 min (internal temp rose to −47° C.). The pale yellow reaction was then stirred overnight as the acetone/dry ice bath expired (15 hrs). The resulting yellow homogeneous solution was washed with 5 M NH4Cl (2×50 mL), and the organic layer was dried (Na2SO4), filtered, and concentrated to provide the crude title compound as a clear dark yellow oil.

Provenance & Evidence