Hydrochloric Acid → 2-Bromoimidazo[5,1-b]thiazole

Temperature

105 °C

2-Bromoimidazo[5,1-b]thiazole-7-carboxylic acid (0.52 g, 2.10 mmol) was suspended in a mixed solvent composed of water (4.0 ml) and acetic acid (6.0 ml). Concentrated hydrochloric acid (0.30 g, 3.04 mmol) was added to the suspension at room temperature, and the mixture was stirred at 105° C. for about 19 hr. After the completion of the reaction, sodium carbonate (0.44 g, 4.15 mmol) was added to the reaction solution, and the mixture was concentrated by removal of the solvent by distillation under the reduced pressure. Water (10 ml) was added to the concentrate. Further, the solvent was removed by distillation under the reduced pressure, and water (10 ml) and ethyl acetate (5 ml) were again added thereto. The mixture was adjusted to pH 6 by the addition of a 2 M aqueous solution of sodium hydroxide with stirring. After the separation, the aqueous layer was extracted twice with 5 ml of ethyl acetate. Thereafter, the organic layers were combined and were washed with 15 wt % brine (5 ml). While concentrating the washed organic layers, the solvent was replaced with methanol (3 ml), and 10 ml of water was added thereto to crystallize 2-bromoimidazo[5,1-b]thiazole. The crystallizing liquid was cooled to 5° C. or below and was stirred overnight. The crystals were then collected by filtration. The resultant precipitate was dried under the reduced pressure to give 2-bromoimidazo[5.1-b]thiazole (0.39 g, yield 91.4%) 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 (10 ml) was added to the concentrate
4. customFurther, the solvent was removed by distillation under the reduced pressure, and water (10 ml) and ethyl acetate (5 ml)
5. additionwere again added
6. additionThe mixture was adjusted to pH 6 by the addition of a 2 M aqueous solution of sodium hydroxide
7. stirringwith stirring
8. customAfter the separation
9. extractionthe aqueous layer was extracted twice with 5 ml of ethyl acetate
10. washwere washed with 15 wt % brine (5 ml)
11. concentrationWhile concentrating the washed organic layers
12. additionwas added
13. customto crystallize 2-bromoimidazo[5,1-b]thiazole
14. temperatureThe crystallizing liquid was cooled to 5° C. or below
15. stirringwas stirred overnight
16. filtrationThe crystals were then collected by filtration
17. dry with materialThe resultant precipitate was dried under the reduced pressure

ORD record

ord-01e9bcbc01874820956c56bfa0151546

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662841B2