Methyl 2-Bromo-5-chlorobenzoate → 1-(2-Bromo-5-chlorophenyl)-4,4,5,5,5-pentafluoropentan-1-one

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Reaction Conditions

Reaction Steps

A THF solution of sodium bis(trimethylsilyl)amide (1.0M, 10 mL, 10 mmol) was added dropwise to a −78° C. THF (20 mL) solution containing methyl 2-bromo-5-chlorobenzoate (0.836 g, 3.35 mmol) and 3,3,4,4,4-pentafluoropentanoic acid (0.644 g, 3.35 mmol, intermediate from Step A). After stirring for 15 minutes at −78° C. the solution was warmed to 0° C. and stirred for an additional 2 hours. The reaction was quenched with an excess of aqueous 1N HCl(ca 20 mL) and stirred overnight at room temperature. The solution was concentrated to remove the majority of the THF. The solution was then diluted with EtOAc and washed with 1N NaHCO3 (twice) and brine. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated compound (liquid). 1H NMR (500 MHz, CH3 CN-d3): δ 7.64 (d, J=8.6 Hz, 1H); 7.56 (d, J=2.6 Hz, 1H); 7.40 (dd, J=8.5, 2.7 Hz, 1H); 3.23 (t, J=7.3 Hz, 2H); 2.61-2.50 (m, 2H). m/z=365.1 (M+H).

Provenance & Evidence