Triethylamine → 1-[(4-Fluoro-2-methylphenyl)carbamoyl]cyclopropanecarboxylic acid

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Reaction Steps

Cyclopropane-1,1-dicarboxylic acid (1.0 g, 8.0 mmol) was suspended in tetrahydrofuran (20 mL), and triethylamine (1.1 mL, 8.0 mmol) was added. After stirring at room temperature for 1 hr, the mixture was cooled in an ice bath. Under ice-cooling, thionyl chloride (0.58 mL, 8.0 mmol) was added dropwise, and the mixture was stirred as it was for 30 min. To this mixture was dropwise added a solution of 4-fluoro-2-methylaniline (3.9 g, 31 mmol) in tetrahydrofuran (2.0 mL) under ice-cooling, and the reaction mixture was warmed to room temperature and stirred overnight. An aqueous sodium hydroxide solution (1N, 50 mL) was added, and the mixture was washed twice with ethyl acetate. The aqueous layer was acidified with hydrochloric acid (1N), and the mixture was extracted twice with ethyl acetate. The mixed organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Hexane-ethyl acetate was added to the residue, and the precipitate was collected by filtration to give the title compound (1.1 g, 60%) as a white solid.

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