Methanol → 3-Cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionamide

Temperature

0 °C

A solution 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid (304 mg, 1.0 mmol) in methylene chloride (10 mL) and N,N-dimethylformamide (1 drop) was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (1.5 mL, 3.0 mmol). The reaction was stirred for 30 min at 0° C. At this time, 1,1,1,3,3,3-hexamethyldisilazane (2.0 mL, 9.5 mmol) was added to the reaction mixture. The reaction was allowed to slowly warm to 25° C. and then stirred at 25° C. for 16 h. The reaction mixture was then treated with methanol (3 mL) and diluted with methylene chloride (35 mL). The resulting mixture was washed with a 5% aqueous sulfuric acid solution (2×10 mL), water (1×25 mL), and a saturated aqueous sodium chloride solution (3×25 mL). The organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionamide (333 mg, 92.5%) as a pale yellow oil: EI-HRMS m/e calcd for C15H17F4NO (M+) 303.1246, found 303.1252.

1. temperatureto slowly warm to 25° C.
2. stirringstirred at 25° C. for 16 h
3. washThe resulting mixture was washed with a 5% aqueous sulfuric acid solution (2×10 mL), water (1×25 mL)
4. dry with materialThe organic layers were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-72ccd42f88da44d7bb93379e7f674e06

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1