反应详情

温度

-5 °C

Concentrated nitric acid (4 mL) was slowly added to 5-bromo-4-isopropyl-thiazol-2-ylamine (2.05 g, 9 mmol), and concentrated phosphoric acid (14 mL) was added dropwise over five minutes. The mixture was cooled to −5° C., and a solution of sodium nitrite (0.768 g, 11 mmol) in 5 mL water was added dropwise over a 15 minute period. The reaction mixture was stirred at −5° C. for 30 minutes, and an aqueous solution of H3PO2 (6 mL, 50% weight in water) was slowly added. The reaction mixture was stirred at −5° C. for 2.5 hours, then stirred at room temperature for 18 hours. The reaction mixture was cooled to 0° C. and quenched by addition of aqueous NaOH (30% weight solution). The mixture was extracted with methylene chloride, and the combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was chromatographed (10% EtOAc in hexanes) to give 236 mg of 5-bromo-4-isopropyl-thiazole as an oil, MS (M+H)=207.

1. additionwas added dropwise over five minutes
2. stirringThe reaction mixture was stirred at −5° C. for 2.5 hours
3. stirringstirred at room temperature for 18 hours
4. temperatureThe reaction mixture was cooled to 0° C.
5. customquenched by addition of aqueous NaOH (30% weight solution)
6. extractionThe mixture was extracted with methylene chloride
7. washthe combined organic extracts were washed with brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe resulting oil was chromatographed (10% EtOAc in hexanes)