Triethylamine → 1-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic Acid

Participants

Reaction Conditions

Reaction Steps

A solution of 1,1-cyclopropanedicarboxylic acid (3.07 g, 23.60 mmol) in THF (40 mL) was cooled to 0° C. and treated with Et3N (3.30 mL, 23.7 mmol) and thionyl chloride (1.72 mL, 23.6 mmol). The resultant reaction mixture was stirred 30 min at 0° C. 4-Fluoroaniline (2.30 mL, 23.9 mmol) was added and the reaction mixture was allowed to slowly warm to RT overnight. The slurry was diluted with EtOAc (200 mL) and was extracted into 1 N aq NaOH (3×60 mL). The aqueous portion was washed with ether (50 mL) and acidified to pH 1-2 with 6 N aq HCl. The resulting precipitate was collected by filtration and washed with water. The remaining solids were dissolved in a mixture of acetonitrile-MeOH and the solution was concentrated in vacuo until precipitation began. Complete dissolution was affected by warming to 70° C. The resultant solution was allowed to cool to RT overnight to provide large crystals. The crystals were isolated by filtration, washed with acetonitrile and dried in vacuo to provide 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (1.76 g). The mother liquors were concentrated to initiate a second crystallization, which provided an additional crop of 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (1.39 g, 60% yield overall). 1H NMR (400 MHz, DMSO-d6): δ 13.06 (s, 1H), 10.55 (s, 1H), 7.60 (m, 2H), 7.12 (m, 2H), 1.39 (s, 4H); MS (ESI) m/z: 224.1 (M+H+).

Provenance & Evidence