Aniline → 5-Fluoro-2-nitro-N-phenylaniline

Temperature

-78 °C

To a solution of aniline (30.1 mL, 0.33 mol) in THF (300 mL) at −78° C. was added LiHMDS (408 mL, 1 M in THF, 0.41 mmol) at such a rate that T≦−65° C. The reaction mixture was stirred at −78° C. for 30 min and was then added to a solution of 2,4-difluoronitrobenzene (50 g, 0.31 mol) in THF (200 mL) at −78° C. at such a rate that T≦−65° C. The mixture was stirred at −78° C. for 2 h. The reaction mixture was diluted with water (300 mL) and EtOAc (300 mL) and the emulsion which formed filtered through Celite®. The layers were separated and the aqueous fraction extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was stirred with pentane (300 mL) for 16 h then filtered to give the title compound as a tan solid. (50 g, 68%). 1H NMR 400 MHz (CDCl3) δ: 9.64 (1H, br s), 8.26 (1H, dd, J=9.5, 6.0 Hz), 7.49-7.42 (2H, m), 7.32-7.25 (3H, m), 6.80 (1H, dd, J=11.3, 2.5 Hz), 6.51-6.45 (1H, m)

1. stirringThe mixture was stirred at −78° C. for 2 h
2. customthe emulsion which formed
3. filtrationfiltered through Celite®
4. customThe layers were separated
5. extractionthe aqueous fraction extracted with EtOAc (3×100 mL)
6. washThe combined organic extracts were washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. stirringThe resultant residue was stirred with pentane (300 mL) for 16 h
10. filtrationthen filtered

ORD record

ord-ff53e359c84e4a78b4ef0fcd6700d213

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2