反应详情

A suspension of 2,4-dibromo-1,3-thiazole-5-carboxylic acid (16.33 g, 56.91 mmol) in dry DCM (250 mL) and DMF (0.400 mL) was cooled in an ice bath. Thionyl chloride (40.0 mL, 548 mmol) was added dropwise. The cooling bath was removed and the suspension was stirred at rt for 2.5 hours. Toluene (80 mL, 800 mmol) was added and the suspension was heated to reflux for 1 hour. The mixture was cooled to room temperature, the solvent was removed and the residue was azeotroped with toluene (2×100 mL) to give a crude intermediate. This material was suspended in DCM (230 mL) and cooled in an ice bath. N,N-Dimethylaminopyridine (0.70 g, 5.7 mmol) was added, followed by the slow addition of 8.5 M ammonium hydroxide in water (100.0 mL, 850.0 mmol). The mixture was stirred at room temperature overnight. The mixture was filtered and the aqueous layer was separated and extracted with DCM (3×100 mL). The combined DCM layers were washed with water, brine, dried over Na2SO4, filtered, and evaporated to give a solid product (11.2 g, 69%). LCMS: (FA) ES+ 287 and ES− 285.

1. temperaturewas cooled in an ice bath
2. customThe cooling bath was removed
3. temperaturethe suspension was heated
4. temperatureto reflux for 1 hour
5. temperatureThe mixture was cooled to room temperature
6. customthe solvent was removed
7. customthe residue was azeotroped with toluene (2×100 mL)
8. customto give a crude intermediate
9. temperaturecooled in an ice bath
10. stirringThe mixture was stirred at room temperature overnight
11. filtrationThe mixture was filtered
12. customthe aqueous layer was separated
13. extractionextracted with DCM (3×100 mL)
14. washThe combined DCM layers were washed with water, brine
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. customevaporated