Ethyl 2-chloro-4-phenyl-1,3-thiazole-5-carboxylate → 2-Chloro-4-phenylthiazole-5-carboxylic acid

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Reaction Steps

A mixture of 2-Chloro-4-phenyl-thiazole-5-carboxylic acid ethyl ester (1 g, 3.74 mmol) in tetrahydrofuran (10 ml) and NaOH (15%, 4.8 ml) was stirred at room temperature for 2 hr. After removal of tetrahydrofuran, the aqueous was neutralized with aqueous hydrochloric acid (3 N) to ˜pH=3. The solid was filtered and washed with water, dried in air to give 2-chloro-4-phenyl-thiazole-5-carboxylic acid (0.83 g). The acid was then dissolved in acetonitrile, and EDC (0.62 g, 4 mmol) was added. The mixture was stirred under an ammonia balloon for 2 hrs. Acetonitrile was removed, the residue was diluted with ethyl acetate and washed with water. Ethyl acetate solution was dried over MgSO4. After removal of MgSO4 and solvent, the residue was diluted with tetrahydrofuran (10 ml), followed by adding triethyl amine (0.5 ml). The mixture was cooled in ice, and trifluoroacetic anhydride (0.85 ml) was added dropwise. After the addition, the reaction mixture was stirred overnight at RT. The mixture was then diluted with ethyl acetate and washed with sat. sodium bicarbonate, dried over MgSO4. After removal of the magnesium sulfate and solvent, the residue was purified on Isco (0-20% gradient ethyl acetate in hexane) to give product (287.9 mg, yield 35% overall). 1H-NMR (CDCl3) 8.07-8.13 (m, 2H); 7.47-7.53 (m, 3H); 4.11 (q, 1H); 1.22 (t, 3H). MS M/z 221 (M+1)

Provenance & Evidence