1,1,3-Trichloroacetone → 5-Bromo-4-(dichloromethyl)-2-methyl-1,3-thiazole

To a solution of 1,1,3-trichloroacetone (30.0 g, 185.85 mmol) in acetone (80.0 mL) was added thioacetamide (18.15 g, 241.60 mmol) and stirred at room temperature overnight. The mixture was then concentrated and re-dissolved in concentrated HCl (30.0 mL) and stirred initially at room temperature for 1 h followed by heating to 55° C. for 70 h. The system was cooled to room temperature, poured into ice water, extracted with EtOAc, dried over sodium sulfate and concentrated. The crude reaction mixture was purified using normal phase conditions (0%→20% EtOAc: hexanes) to afford a pale yellow solid. To this solid (13.9 g, 76.0 mmol) in acetic acid (109 mL) was added bromine (5.90 mL, 115 mmol) and the system was stirred at room temperature overnight. The mixture was poured into ice water, extracted with EtOAc, dried over sodium sulfate and concentrated. The crude reaction mixture was purified using normal phase conditions (5% EtOAc:hexanes) to afford the title compound (2-4) as a bone powder. ESI+ MS: 261.9 [M+H]+.

1. concentrationThe mixture was then concentrated
2. dissolutionre-dissolved in concentrated HCl (30.0 mL)
3. stirringstirred initially at room temperature for 1 h
4. temperatureby heating to 55° C. for 70 h
5. temperatureThe system was cooled to room temperature
6. additionpoured into ice water
7. extractionextracted with EtOAc
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated
10. customThe crude reaction mixture
11. customwas purified
12. customto afford a pale yellow solid
13. stirringthe system was stirred at room temperature overnight
14. extractionextracted with EtOAc
15. dry with materialdried over sodium sulfate
16. concentrationconcentrated
17. customThe crude reaction mixture
18. customwas purified

ORD-Eintrag

ord-036fb5d6ac5c468186faa3416fe4a3e9

Quelldatensatz

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08030495B2