反应详情

A mixture of 3,5-dichloroisothiazole-4-carbonitrile (5.37 g, 30 mmol), 4-(tertbutoxycarbonylamino)phenylboronic acid (14.22 g, 60 mmol), potassium fluoride (6.11 g, 105 mmol), 18-crown-6 (3.96 g, 15 mmol), and palladium acetate (337 mg, 1.5 mmol) in toluene (250 ml) was heated at reflux for 6 hours. The reaction was cooled to RT and the mixture was diluted with water and EtOAc. Layers were separated and the aqueous layer was extracted with EtOAc×3. The combined organics was washed with brine and dried with MgSO4, filtered, and concentrated. The crude product was purified by flash silica gel column eluted with 5-15% EtOAc in hexanes to obtain the above compound as a white crystalline solid (8.55 g, 85%). NMR and MS spectra are consistent with the structure. HPLC purity 97.6%.

1. temperaturewas heated
2. temperatureat reflux for 6 hours
3. customLayers were separated
4. extractionthe aqueous layer was extracted with EtOAc×3
5. washThe combined organics was washed with brine
6. dry with materialdried with MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by flash silica gel column
10. washeluted with 5-15% EtOAc in hexanes