Aniline → 3,5-Difluoro-n-phenylaniline

Temperature

90 °C

In a 5 mL microwave reaction vial was placed aniline (0.298 g. 3.20 mmol) and 1,3-difluoro-5-iodobenzene (0.768 g, 3.20 mmol) in toluene (3 mL). KOH (0.323 g, 5.76 mmol) in water (650 μL) and N,N,N-trimethylhexadecan-1-aminium bromide (6.30 mg, 0.017 mmol) were added to the vial with stirring. After the reaction was warmed to 90° C., bis[tri(t-butylphosphine]palladium[0] (0.016 g, 0.032 mmol) was added and the reaction was stirred at 150° C. for 4 h and then 160° C. for 2 h. The mixture was diluted with water and brine, and extracted with toluene. The toluene extract was subsequently washed with water, dried over MgSO4 and concentrated. The residue was purified by flash column chromatography to provide the title compound as a brown oil (0.132 g). LCMS m/z=206.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 6.54 (tt, J=9.35, 2.27 Hz, 1H), 6.63 (dd, J=10.48, 2.15 Hz, 2H), 7.01 (dt, J=14.65, 1.14 Hz, 1H), 7.17 (dd, J=8.59, 1.01 Hz, 2H), 7.34 (t, J=7.83 Hz, 2H), 8.69 (s, 1H).

1. customIn a 5 mL microwave reaction
2. stirringthe reaction was stirred at 150° C. for 4 h
3. extractionextracted with toluene
4. extractionThe toluene extract
5. washwas subsequently washed with water
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified by flash column chromatography

ORD record

ord-608f679dbbd647098ca57e81b68c3f0e

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895776B2