Water → tert-Butyl 4-(3-((5-(trifluoromethyl)pyridin-2-yl)oxy)benzylidene)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

[3-(5-Trifluoromethyl-pyridin-2-yloxy)-benzyl]-phosphonic acid diethyl ester (2.3 g, 6.0 mmol) from Step 3 and 1,4,7,10,13-pentaoxacyclopentadecane (15-Crown-5, 0.03 mL, 0.15 mmol) were combined in THF (10 mL). The mixture was cooled to 0° C. and sodium hydride (240 mg, 60% dispersion in mineral oil, 6.0 mmol) was added. The reaction was warmed to room temperature, stirred for 30 minutes and then cooled back to 0° C. A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.2 g, 6.0 mmol) in THF (6 mL) was added and the reaction was warmed to room temperature. After 16 hours, water was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×200 mL) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to a thick oil. Treatment of the oil with hot isopropyl ether (45 mL) provided the title compound as a white solid (1.88 g). 1H NMR (400 MHz, CD3OD) δ ppm 1.46 (s, 9H) 2.34 (td, J=5.85, 1.18 Hz, 2H) 2.46 (td, J=5.87, 1.07 Hz, 2H) 3.37-3.44 (m, 2H) 3.45-3.57 (m, 2H) 6.41 (s, 1H) 6.92-7.04 (m, 2H) 7.06-7.17 (m, 2H) 7.31-7.54 (m, 1H) 8.08 (ddd, J=8.74, 2.59, 0.56 Hz, 1H) 8.42 (td, J=1.73, 0.90 Hz, 1H).

Provenance & Evidence