反应详情

温度

47.5 °C

Acetonitrile (9 L) was sparged with nitrogen for 2 hours. To the solvent was added cesium fluoride (335.8 g, 2.21 mol), 4-(tributylstannyl)pyridazine (408 g, 1.11 mol), 4-trifluoromethyl-6-iodophenol (318.3 g, 1.11 moles), palladium tetrakis 25 triphenylphosphine (61.31 g, 53.05 mmol) and copper (I) iodide (40 g, 210 mmol) at 20° C. The resulting orange suspension was heated to 45-50° C. for 2 hours. The reaction was cooled and partitioned between TBME (2×5 L) and aqueous hydrochloric acid solution (2 N, 2×5 L). The resulting biphasic solution was filtered and the layers separated. The aqueous phases were combined and basified with a sodium hydroxide solution (4 M, 6 L) to obtain a pH=4-5. The resulting suspension was extracted with EtOAc (10 L) and the organic layer concentrated in vacuo to afford the title compound as an orange solid (60%).

1. customAcetonitrile (9 L) was sparged with nitrogen for 2 hours
2. temperatureThe reaction was cooled
3. custompartitioned between TBME (2×5 L) and aqueous hydrochloric acid solution (2 N, 2×5 L)
4. filtrationThe resulting biphasic solution was filtered
5. customthe layers separated
6. customto obtain a pH=4-5
7. extractionThe resulting suspension was extracted with EtOAc (10 L)
8. concentrationthe organic layer concentrated in vacuo