Citric Acid → 2-(2-fluoro-pyridin-4-yl)-2-(N-acetyl-cyclopentylamino)-1-(3-trifluoromethyl-phenyl)-ethanol

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 2-(2-fluoro-pyridin-4-yl)-2-cyclopentylamino-1-(3-trifluoromethyl-phenyl)-ethanol (6) (1.0 g, 2.7 mmol) and diisopropylamine (0.95 mL, 5.4 mmol) in methylene chloride (10 mL) was placed under argon and cooled to −10° C. Acetyl chloride (0.21 mL, 3.0 mmol) in methylene chloride (1.0 mL) was slowly added to the reaction mixture. After 2 hrs, ethyl acetate was added (200 mL) followed by aqueous citric acid (50 mL of a 10% solution). The organic layer was then washed with aqueous sodium bicarbonate (50 mL of a sat. solution) and water (50 mL), dried (sodium sulfate), filtered, and concentrated. The crude residue was passed though a pad a silica gel (50% ethyl acetate in hexane) to remove minor impurities, and taken to the next step. Colorless oil (95%): 1H NMR (300 MHz, CDCl3) d 8.54 (d, J=5.1 Hz, 1 H, Pyr), 7.49 (m, 4 H, Ar), 6.81 (d, J=5.0Hz, 1 H, Pyr), 6.72 (s, 1 H, Pyr), 5.63 (s, 1 H, OH), 5.46 (s, 1 H, PhCHOH), 4.34 (s, 1 H, CHCHN), 4.16 (m, 1 H, CH2CHCH2), 2.32 (s, 3 H, COCH3), 1.90 (m, 1 H, CH2), 1.60 (m, 7 H, CH2).

Provenance & Evidence