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

Temperature

90 °C

Toluene (1.0 L) was added to 104 g of 5-bromo-2-formylaminomethylthiazole, and the mixture was heated to 90° C. and was stirred. A solution of 65.8 g of phosphorus oxychloride in 100 ml of toluene was added to the reaction mixture, and the mixture was stirred at that temperature for 1.5 hr. After standing to cool, 2 L of a 0.5 N aqueous hydrochloric acid solution was added, and the aqueous layer was separated. The aqueous layer was adjusted to pH 6.2 by the addition of a 5 N aqueous sodium hydroxide solution and was extracted with 1.5 L of ethyl acetate and then with 1.0 L of ethyl acetate. The organic layers were combined, were washed with a 5% aqueous sodium bicarbonate solution and a 20% aqueous sodium chloride solution in that order, and were dried over anhydrous magnesium sulfate. The solvent was removed to bring the volume to about 100 ml, 500 ml of ethyl acetate:hexane=1:4 solution was added thereto, and the mixture was stirred in an ice-water bath for crystallization to give 57.6 g of 2-bromimidazo[5,1-b]thiazole.

1. stirringthe mixture was stirred at that temperature for 1.5 hr
2. temperatureto cool
3. customthe aqueous layer was separated
4. additionThe aqueous layer was adjusted to pH 6.2 by the addition of a 5 N aqueous sodium hydroxide solution
5. extractionwas extracted with 1.5 L of ethyl acetate
6. washwere washed with a 5% aqueous sodium bicarbonate solution
7. dry with materiala 20% aqueous sodium chloride solution in that order, and were dried over anhydrous magnesium sulfate
8. customThe solvent was removed
9. additionhexane=1:4 solution was added
10. stirringthe mixture was stirred in an ice-water bath for crystallization

ORD record

ord-64c5115226264193a440122c238141f9

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07524951B2