Water → 2-Bromoimidazo[5,1-b]thiazole

Temperature

105 °C

2-Bromoimidazo[5,1-b]thiazole-7-carboxylic acid (34.8 g, 141 mmol) was suspended in a mixed solvent composed of water (320 ml) and acetic acid (480 ml). Concentrated sulfuric acid (29.5 g, 301 mmol) was added to the suspension at room temperature, and the mixture was stirred at 105° C. for about 24 hr. After the completion of the reaction, sodium carbonate (35.1 g, 331 mmol) was added to the reaction solution, and the mixture was concentrated by removal of the solvent by distillation under the reduced pressure. Water (320 ml) was added to the concentrate, and the solvent was removed by distillation under the reduced pressure. Thereafter, water (200 ml) and ethyl acetate (400 ml) were again 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 extracted with ethyl acetate twice (200 ml, 100 ml). The organic layers were combined and were washed with 15 wt % brine (100 ml). After washing, while concentrating the washed organic layers, the solvent was replaced with hexane to crystallize 2-bromoimidazo[5,1-b]thiazole. The crystallizing liquid was cooled to 5° C. or below and was stirred overnight, and the crystals were collected by filtration. The crystals were washed with hexane (80 ml) and were dried under the reduced pressure to give 2-bromoimidazo[5,1-b]thiazole (26.0 g, yield 90.8%) as a white solid.

1. additionwas added to the reaction solution
2. concentrationthe mixture was concentrated by removal of the solvent by distillation under the reduced pressure
3. additionWater (320 ml) was added to the concentrate
4. customthe solvent was removed by distillation under the reduced pressure
5. additionThereafter, water (200 ml) and ethyl acetate (400 ml) were again 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 extracted with ethyl acetate twice (200 ml, 100 ml)
11. washwere washed with 15 wt % brine (100 ml)
12. washAfter washing
13. concentrationwhile concentrating the washed organic layers
14. customto crystallize 2-bromoimidazo[5,1-b]thiazole
15. temperatureThe crystallizing liquid was cooled to 5° C. or below
16. stirringwas stirred overnight
17. filtrationthe crystals were collected by filtration
18. washThe crystals were washed with hexane (80 ml)
19. customwere dried under the reduced pressure

ORD record

ord-8fe51ad61e9f40a69451e0f6c0d8d374

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662841B2