Water → 2-Bromoimidazo[5,1-b]thiazole

Temperature

105 °C

Ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate (2.00 g, 7.3 mmol) was suspended in a mixed solvent composed of water (16 ml) and acetic acid (24 ml), concentrated sulfuric acid (7.84 g, 80.0 mmol) was added to the suspension at room temperature, and the mixture was stirred at 105° C. for about 30 hr. After the completion of the reaction, sodium carbonate (9.32 g, 88.0 mmol) was added to the reaction solution, and acetic acid was removed by distillation under the reduced pressure. Further, water (10 ml) was again added to the concentrate, and the solvent was removed by distillation under the reduced pressure. Water (10 ml) and ethyl acetate (20 ml) were added to the residue, and the mixture was adjusted to pH 7 by the addition of a 25 wt % aqueous solution of sodium hydroxide with stirring. The insolubles were removed by filtration, followed by separation. The aqueous layer was then extracted twice with ethyl acetate (20 ml, 20 ml). The organic layer was washed with 15 wt % brine (20 ml). After washing, while concentrating the organic layer, the solvent was replaced with n-hexane to crystallize 2-bromoimidazo[5,1-b]thiazole. Subsequently, the suspension was cooled to 5° C. or below and was stirred overnight. The crystals were collected by filtration, were washed with n-hexane (20 ml) and were dried under the reduced pressure to give 2-bromoimidazo[5,1-b]thiazole (1.02 g, yield 68.5%) as a white solid.

1. additionwas added to the suspension at room temperature
2. customwas removed by distillation under the reduced pressure
3. additionFurther, water (10 ml) was again added to the concentrate
4. customthe solvent was removed by distillation under the reduced pressure
5. additionWater (10 ml) and ethyl acetate (20 ml) were added to the residue
6. additionthe mixture was adjusted to pH 7 by the addition of a 25 wt % aqueous solution of sodium hydroxide
7. stirringwith stirring
8. customThe insolubles were removed by filtration
9. customfollowed by separation
10. extractionThe aqueous layer was then extracted twice with ethyl acetate (20 ml, 20 ml)
11. washThe organic layer was washed with 15 wt % brine (20 ml)
12. washAfter washing
13. concentrationwhile concentrating the organic layer
14. customto crystallize 2-bromoimidazo[5,1-b]thiazole
15. temperatureSubsequently, the suspension was cooled to 5° C. or below
16. stirringwas stirred overnight
17. filtrationThe crystals were collected by filtration
18. washwere washed with n-hexane (20 ml)
19. customwere dried under the reduced pressure

ORD record

ord-9a4ea3b82393471bb85ded563926e9bc

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662841B2