4-Iodo-2-methylthiazole synthesis

Yield:872363-16-1 47%

Reaction Conditions:

Stage #1: 4-bromo-2-methyl-1,3-thiazolewith n-butyllithium in diethyl ether;hexane at -78; for 1 h;
Stage #2: 1,1-diiodoethane in diethyl ether;hexane at -78 - 20; for 2.5 h;

Steps:

73.73(B)

73 (B) 4-Iodo-2-methylthiazole ;To a solution of 4-bromo-2-methylthiazole (2.0 g, 11 mmol) in anhydrous Diethyl ether (44 mL) was added dropwise at-78°C, 5.30 mL of BuLi 2.5M in hexane. The mixture was stirred for lh at-78°C. A solution of diiodoethane (6.20 g, 22 mmol) in 27 mL of Diethyl ether was added dropwise at-78°C to the reaction mixture. The resulting solution was stirred 30 min at-78°C and slowly warmed to room temperature over a period of 2h. The reaction cooled with a ice bath at-10°C and quenched with water. The two layers were separated; the aqueous layer was extracted with Diethyl ether. The combined organic layers were dried over Na2S04, filtered and concentrated under medium pressure. The crude product was purified by flash chromatography (Prepacked 10 g silicagel column with Pentane/ Diethyl ether : 95/5 as eluent) to afford 1.17 g of 4-iodo-2-methylthiazole (Yield: 47%) as a colorless oil. LCMS (RT) : 3.49min; MS (ES+) gave m/z : 225.0

References:

WO2005/123703,2005,A2 Location in patent:Page/Page column 130