Ethyl chloroformate → 2-Chloro-4-(4-trifluoromethylphenyl)thiazole-5-carboxylic acid ethyl ester

Participants

Reaction Steps

To a solution of 5.0 g (19.0 mmole) of 2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole and 57 mL of tetrahydrofuran at −78 degrees, was added, over 10 minutes, 9.5 mL of 2.5 M n-butyl lithium in hexanes solution. After 30 minutes, 1.1 mL of 2.5 M n-butyl lithium in hexanes solution was added The mixture was stirred for 2 hours and then 10.63 mL (107.8 mmole) of ethyl chloroformate was added quickly to a rapidly stirring solution. After 15 minutes, the cooling bath was removed and the mixture was stirred at room temperature for 22 minutes. The reaction was quenched by the addition of 75 mL of 1M hydrochloric acid, stirred for 5 minutes and then diluted with 500 mL of ethyl acetate. The ethyl acetate layer was washed twice with 75 mL of water, once with 75 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting dichloromethane-hexanes (gradient 10:90-50:50) to give 4.94 g of 2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester as a light yellow solid.

Provenance & Evidence