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

Participants

Reaction Steps

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]+.

Provenance & Evidence