反应详情

3-Iodo-5-nitro-2′-trifluoromethyl-biphenyl-4-ylamine (466 mg, 1.14 mmol, as prepared in Example 9, step A), (Ph3P)2PdCl2 (0.05 eq., 40.1 mg, 0.057 mmol), and CuI (0.05 eq., 10.2 mg, 0.054 mmol) were placed in a 40 mL vial equipped with a magnetic stir bar. The vial was evacuated and backflushed with Ar, and anhydrous THF (6 mL) and TEA (4.0 eq., 0.64 mL, 4.56 mmol) were added via syringe. Propargyl alcohol (4 eq., 0.270 mL, 4.56 mmol) was added via syringe, and the reaction was stirred at RT for 16 h. The solution was diluted with EtOAc (20 mL) and filtered. The solvent was removed under reduced pressure, and the crude product was purified by column chromatography on a 24-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 3:2, v/v over 20 min, yielding 279 mg (73%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 8.10 (d, J=2.0 Hz, 1H), 7.73 (d, J=7.6 Hz, 1H), 7.53-7.59 (m, 1H), 7.53 (d, J=1.8 Hz, 1H), 7.43-7.51 (m, 1H), 7.29 (d, J=7.6 Hz, 1H), 6.82 (br. s., 2H), 4.59 (s, 2H).

1. customvial equipped with a magnetic stir bar
2. customThe vial was evacuated
3. additionwere added via syringe
4. filtrationfiltered
5. customThe solvent was removed under reduced pressure
6. customthe crude product was purified by column chromatography on a 24-g SiO2 pre-packed column
7. washeluting with EtOAc/hexanes, 0:1 to 3:2, v/v over 20 min