Acetonitrile → 3-Chloro-5-nitro-2'-trifluoromethyl-biphenyl-4-ylamine

Temperature

80 °C

The procedure of Nickson, T. E. et al. (Synthesis 1985, 669-670) was used. 3-Nitro-2′-trifluoromethyl-biphenyl-4-ylamine (12.7 g, 45.0 mmol, as prepared in the previous step) was placed in a 250 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser, and dry acetonitrile (150 mL) was added. The solid was allowed to dissolve, and NCS (1.5 eq., 9.02 g, 67.5 mmol) was added as a solid. The reaction was heated at 80° C. for 3 days. The reaction was cooled to RT, diluted with EtOAc, then washed twice with water (20 mL) and once with brine (30 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The crude material was chromatographed on an 80-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 30 min, yielding 6.96 g (49%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 8.10 (d, J=2.0 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.57-7.62 (m, 1H), 7.56 (d, J=1.8 Hz, 1H), 7.44-7.54 (m, 1H), 7.32 (d, J=7.3 Hz, 1H), 6.64 (br. s., 2H).

1. customet al. (Synthesis 1985, 669-670)
2. customwas placed in a 250 mL round-bottom flask
3. customequipped with a magnetic stir bar and a reflux condenser
4. dissolutionto dissolve
5. temperatureThe reaction was cooled to RT
6. washwashed twice with water (20 mL) and once with brine (30 mL)
7. dry with materialThe combined organic extracts were dried over MgSO4
8. filtrationfiltered
9. customthe solvent was removed under reduced pressure
10. customThe crude material was chromatographed on an 80-g SiO2 pre-packed column
11. washeluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 30 min

ORD record

ord-a86823ffc4814d3490376b4be3ba297d

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08232409B2