Hydrochloric Acid → N-(4-Ethylphenyl)-2,3,5,6-tetrafluoroaniline

4-Ethylaniline (242.36 g; 2.00 mol) is dissolved in dry tetrahydrofuran (900 ml). A solution of n-BuLi (2.5 M in hexanes, 800 ml; 2.00 mol) is added under N2 with cooling maintaining the reaction temperature below 15°. After stirring for 1 hour at 10°, neat pentafluorobenzene (168.06 g; 1.00 mol) is added with cooling to the mixture, keeping the temperature at 10–20°. The reaction is stirred at ambient temperature for 1.5 hours, then aqueous HCl (6 N; 500 ml) is added slowly with vigorous stirring and cooling, keeping the reaction temperature below 35°. The quenched reaction is stirred at ambient temperature for 0.5–18 hours. The aqueous layer is separated, and the organic phase is concentrated under reduced pressure (30–150 mm) to one-fourth volume. The concentrate is diluted with heptane (300 ml) and extracted with water (300 ml). The separated top organic layer is stirred over 230–400 mesh silica gel (50 g) and filtered. The filter cake is washed with heptane (4×50 ml). The combined filtrate and washings are concentrated under reduced pressure (20–30 mm) to give solid crude product. This material is recrystallized from hot heptane (200 ml) and collected at 0°. This solid is washed with cold heptane (100 ml) and dried under reduced pressure at 40° to give pure N-(2′,3′,5′,6′-tetrafluorophenyl)-4-ethylaniline.

1. temperaturewith cooling
2. temperaturemaintaining the reaction temperature below 15°
3. temperaturewith cooling to the mixture
4. customat 10–20°
5. stirringThe reaction is stirred at ambient temperature for 1.5 hours
6. stirringwith vigorous stirring
7. temperaturecooling
8. customthe reaction temperature below 35°
9. customThe quenched reaction
10. stirringis stirred at ambient temperature for 0.5–18 hours
11. customThe aqueous layer is separated
12. concentrationthe organic phase is concentrated under reduced pressure (30–150 mm) to one-fourth volume
13. additionThe concentrate is diluted with heptane (300 ml)
14. extractionextracted with water (300 ml)
15. stirringThe separated top organic layer is stirred over 230–400 mesh silica gel (50 g)
16. filtrationfiltered
17. washThe filter cake is washed with heptane (4×50 ml)
18. concentrationThe combined filtrate and washings are concentrated under reduced pressure (20–30 mm)
19. customto give solid crude product
20. customThis material is recrystallized from hot heptane (200 ml)
21. customcollected at 0°
22. washThis solid is washed with cold heptane (100 ml)
23. customdried under reduced pressure at 40°

ORD record

ord-8310bdc4e69046709e27dcf15ee6fc08

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07115662B2