4-Amino-1-Boc-piperidine → HCID 67195753, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 4-(5-bromo-pyridin-2-yl)-morpholine (4.47 g, 18.39 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.42 g, 22.07 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (5.16 g, 46.00 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.18 g, 0.37 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone)dipalladium(0) (1.52 g, 1.47 mmol, 0.08 equiv). The reaction mixture was stirred under nitrogen at 100° C. for 16 h, cooled to rt, filtered and the filtrate concentrated by evaporation under reduced pressure. The crude material was purified with silica column chromatography eluting with dichloromethane/methanol (20:1+0.5% triethylamine) to provide 1.60 g (24%) of the title compound in 90% purity according to 1H NMR. 1H NMR (400 MHz, CH3OD): δ 1.20-1.37 (m, 2H), 1.46 (s, 9H), 1.95 (dd, J=13.0 Hz, J=2.7 Hz, 2H), 2.94 (br s, 2H), 3.21-3.28 (m, 4H), 3.32-3.41 (m, 1H), 3.73-3.84 (m, 4H), 4.01 (d, J=13.4 Hz, 2H), 6.74 (d, J=9.0 Hz, 1H), 7.12 (dd, J=9.0 Hz, J=2.9 Hz, 1H), 7.68 (d, J=2.7 Hz, 1H). MS (ISP): 363.3 [M+H]+.

Provenance & Evidence