Ethyl 2-chloroacetoacetate → Ethyl 2-anilino-4-methyl-1,3-thiazole-5-carboxylate

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Reaction Steps

To 70 ml of ethanol, 10.7 g (70 mmol) of phenylthiourea and 11.6 g (70 mmol) of ethyl 2-chloro-3-oxobutanate were dissolved, followed by heating under refluxing for 8 hours. The reaction liquid was concentrated and dissolved in ethyl acetate and the organic layer was washed with an aqueous solution of sodium carbonate, water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure. Solid obtained was washed with diisopropyl ether to obtain 16.8 g (yield: 91%) of ethyl 4-methyl-2-(N-phenylamino)thiazole-5-carboxylate. (2) To 50 ml of ethanol, 12.8 g (49 mmol) of ethyl-4-methyl-2-(N-phenylamino)thiazole-5-carboxylate was dissolved, followed by adding 24 g (150 mmol) of 25% sodium hydroxide aqueous solution, and stirring at 80° C. for 15 hours. The reaction liquid was poured into ice water, and acetic acid was added to make acidic. Crystal precipitated was filtered, washed with water and a mixed solvent of hexane/ethyl acetate and dried to obtain 5.50 g (yield: 48%) of 4-methyl-2-(N-phenylamino)thiazole-5-carboxylic acid.

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