Bromine → 5-Bromo-2-methyl-1,3-thiazole-4-carboxylic acid

Temperature

0 °C

2-Methyl-thiazole-4-carboxylic acid (13.0 g, 90.8 mmol) was dissolved in 750 ml THF and cooled to −75° C. n-BuLi (1.6M in THF; 120 ml, 190.7 mmol) was added dropwise in 30 minutes. The red suspension was stirred for 15 min. at −75° C. and 30 min. at 0° C. A solution of bromine (5.1 ml, 100 mmol) in 20 ml cyclohexane was added dropwise at −75° C. and stirring was continued at room temperature for 2 hrs. The reaction mixture was quenched with 20 ml water, evaporated and acidified with 2N HCl to pH 2. The aqueous layer was extracted two times with ethyl acetate. The combined organic extracts were dried with sodium sulfate, filtered and evaporated. The crude product (16.4 g, 81%) [MS: m/e=223.0 (M+H+)] was used without any further purification for the next step.

1. additionwas added dropwise in 30 minutes
2. stirringstirring
3. waitwas continued at room temperature for 2 hrs
4. customThe reaction mixture was quenched with 20 ml water
5. customevaporated
6. extractionThe aqueous layer was extracted two times with ethyl acetate
7. dry with materialThe combined organic extracts were dried with sodium sulfate
8. filtrationfiltered
9. customevaporated
10. customThe crude product (16.4 g, 81%) [MS: m/e=223.0 (M+H+)] was used without any further purification for the next step

ORD record

ord-4dc22af7ee76472da28a558c42dcc540

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07659401B2