[Cl:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[N:6]=1.C([Li])CCC.Cl[C:23]([O:25][CH2:26][CH3:27])=[O:24]>O1CCCC1>[CH2:26]([O:25][C:23]([C:4]1[S:3][C:2]([Cl:1])=[N:6][C:5]=1[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:14])[F:15])[CH:8]=1)=[O:24])[CH3:27]To a solution of 10.1 g (38.3 mmole) of 2-chloro-4-(3-trifluoromethyl-phenyl)-thiazole in 120 mL of tetrahydrofuran at −78 degrees was added over 20 minutes, 20 mL of 2.5 M n-butyl lithium in hexanes. The mixture was stirred for 2 hours and then 19 mL (93.4 mmole) of ethyl chloroformate was added quickly. The mixture was stirred for 15 minutes, then the cooling bath was removed. After 25 minutes, the reaction was quenched by the addition of 150 mL of 1M hydrochloric acid. The mixture was stirred for 5 minutes, and then diluted with 1 L of ethyl acetate. The ethyl acetate layer was washed twice with 150 mL of water, once with 100 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-hexanes (gradient 10:90-50:50) to give 5.62 g of 2-chloro-4-(3-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester as a golden oil.
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