反应详情

温度

25 °C

4-Bromo-3-fluoroaniline (0.95 g, 5.0 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (1.35 g, 9.0 mmol), KF (0.96 g, 16.5 mmol), and Pd2(dba)3 (120 mg, 0.125 mmol) were added to a 50 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. THF (12.5 mL) was added and the mixture was purged with nitrogen for an additional 5 minutes. A solution of tri-t-butylphosphine (10% wt in hexanes) (0.74 mL, 0.25 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 16 hours. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification via Isco chromatography (the Redisep® column, silica, gradient 5%-100% ethyl acetate in hexane) afforded 5-(4-amino-2-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile as a white solid (1.05 g, 98%).

1. customThe flask was sealed
2. custompurged with nitrogen for 5 minutes
3. additionTHF (12.5 mL) was added
4. customthe mixture was purged with nitrogen for an additional 5 minutes
5. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (0.74 mL, 0.25 mmol) was added via syringe
6. additionThe mixture was diluted with 250 mL of EtOAc
7. filtrationfiltered through a plug of silica gel
8. washwashed with 200 mL of EtOAc
9. concentrationconcentrated
10. customto give a crude brown/black semi-solid
11. customPurification via Isco chromatography (the Redisep® column, silica, gradient 5%-100% ethyl acetate in hexane)