反应详情

温度

100 °C

To a suspension of Pd(OAc)2 (11.2 mg, 0.05 mmol, 0.05 equiv) and PPh3 (26.2 mg, 0.1 mmol, 0.1 equiv) in DME (4 mL) were sequentially added 2-butyl-1-(2-hydroxy-2-methylpropyl)-5-iodo-1H-imidazole-4-carbonitrile S5 (347 mg, 1 mmol, 1 equiv), 2-amino-4-methoxycarbonylphenylboronic acid hydrochloride salt (347 mg, 1.5 mmol, 1.5 equiv) and 1.5 M aqueous Na2CO3 (2.0 mL, 3 mmol, 3 equiv) at 25° C. The reaction was heated at 100° C. for 6 h. TLC and MS analysis indicated the presence of S5; consequently, additional Pd(OAc)2 (5 mg) and PPh3 (13 mg) were added and the reaction was heated further at 100° C. for 15 h. The reaction was then cooled down to 25° C. and partitioned between EtOAc (50 mL) and H2O (10 mL). The aqueous layer was extracted with EtOAc (3×15 mL). The combined organic layers was washed with saturated aqueous NaCl (20 mL), dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica gel (1/9 EtOAc/hexanes-7/3 EtOAc/hexanes, gradient) afforded the title compound (118 mg, ˜90% pure, 32%) as light yellow foam, which was used in the next step without further purification.

1. customat 25° C
2. temperaturethe reaction was heated further at 100° C. for 15 h
3. temperatureThe reaction was then cooled down to 25° C.
4. custompartitioned between EtOAc (50 mL) and H2O (10 mL)
5. extractionThe aqueous layer was extracted with EtOAc (3×15 mL)
6. washThe combined organic layers was washed with saturated aqueous NaCl (20 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customPurification by flash column chromatography on silica gel (1/9 EtOAc/hexanes-7/3 EtOAc/hexanes, gradient)