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

Temperature

-78 °C

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).

1. temperaturewas warmed to 0° C.
2. stirringstirred for an additional 2 hours
3. customThe reaction was quenched with an excess of aqueous 1N HCl(ca 20 mL)
4. stirringstirred overnight at room temperature
5. concentrationThe solution was concentrated
6. customto remove the majority of the THF
7. additionThe solution was then diluted with EtOAc
8. washwashed with 1N NaHCO3 (twice) and brine
9. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by silica gel chromatography
13. customto give the indicated compound (liquid)

ORD record

ord-41821529710440ecb91d214793186413

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365574B2