1-(3-Bromo-2-fluorophenyl)-2,2,2-trifluoroethan-1-one synthesis

Yield:-

Reaction Conditions:

Stage #1: o-fluorobromobenzenewith lithium diisopropyl amide in tetrahydrofuran;hexane at -78; for 0.0833333 h;
Stage #2: ethyl trifluoroacetate,with sodium carbonate in tetrahydrofuran;hexane;water at -78; for 1 h;

Steps:

69

To a solution of 1-bromo-2-fluorobenzene (5.0 g, 28.6 mmol) in dry tetrahydrofuran (50 ml) under nitrogen, at-78 °C was added lithium diisopropylamide (2.0 M in hexane, 15.7 ml, 31.4 mmol). The mixture was stirred for 5 minutes after which ethyl trifluoroacetate (3.76 ml, 31.4 mmol) was added and the stirring was continued at-78 °C for an additional hour. The reaction mixture was brought to ambient temperature and water (50 ml) was added. The phases were separated and the aqueous phase extracted with ethylacetate (3x100 ml). The combined organic phases was dried (MgS04) and evaporated to dryness to give an oil. The residue was purified by flash column chromatography (isooctane) to give the title compound (2.38 g). MS m/z (relative intensity, 70 eV) 272 (M+, 11), 270 (M+, 11), 203 (97), 201 (bp, 173 (46).

References:

WO2005/121087,2005,A1 Location in patent:Page/Page column 68-69