Triethylamine → Tert-butyl 3-((2-(4-fluorophenyl)-2-oxoethyl)carbamoyl)piperidine-1-carboxylate

Participants

Reaction Steps

Triethyl amine (1.52 mL, 10.4 mmol) was added dropwise to a solution of piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (600 mg, 2.6 mmol) and 2-amino-1-(4-fluorophenyl)ethanone hydrochloride (500 mg, 2.6 mmol) in THF (12 mL), followed by T3P (propylphosphonic anhydride) (1.7 mL, 2.6 mmol, 50% in EtOAc) at 0° C. The reaction mixture was stirred 30 min, allowed to warm up to room temperature and stirred for an additional 8 h. The reaction mixture was then concentrated under reduced pressure and diluted with EtOAc. The organic layer was washed with aqueous 10% NaHCO3, water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by purified by column chromatography (silica gel 60-120 mesh, eluent 20-25% EtOAc in petroleum ether) to afford tert-butyl 3-((2-(4-fluorophenyl)-2-oxoethyl)carbamoyl)piperidine-1-carboxylate (500 mg, yield 52%). 1H NMR (400 MHz, DMSO-d6) δ 8.33-8.30 (t, J=5.6 Hz, 1H), 8.08-8.04 (dd, J=8.5 Hz, 5.8 Hz, 2H), 7.39-7.35 (t, J=8.7 Hz, 2H), 4.57-4.56 (m, 2H), 3.99-3.86 (m, 2H), 2.39-2.32 (m, 1H), 1.87-1.84 (m, 1H), 1.66-1.62 (m, 1H), 1.56-1.46 (m, 2H), 1.40 (s, 9H), 1.32-1.23 (m, 2H).

Provenance & Evidence