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

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.

1. temperaturethe mixture was cooled in an ice bath
2. temperatureUnder ice-cooling
3. stirringthe mixture was stirred as it
4. waitwas for 30 min
5. temperaturecooling
6. temperaturethe reaction mixture was warmed to room temperature
7. stirringstirred overnight
8. washthe mixture was washed twice with ethyl acetate
9. extractionthe mixture was extracted twice with ethyl acetate
10. dry with materialThe mixed organic layer was dried over anhydrous magnesium sulfate
11. customthe solvent was evaporated under reduced pressure
12. additionHexane-ethyl acetate was added to the residue
13. filtrationthe precipitate was collected by filtration

ORD record

ord-2b9e8d906c0e41babdf7a938fbd90b63

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445509B2