4-Amino-1-Boc-piperidine → HCID 67197045, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 4-bromo-3-fluoro-pyridine (2.98 g, 16.93 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.07 g, 20.31 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (4.75 g, 42.32 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.16 g, 0.34 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone) dipalladium(0) (1.40 g, 1.35 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 a gradient of dichloromethane/methanol (10:0→9:1) and then recrystallized from diethylether to provide 0.20 g (4%) of the title compound in 90% purity according to 1H NMR. 1H NMR (400 MHz, DMSO): δ 1.27-1.38 (m, 2H), 1.40 (s, 9H), 1.82 (d, J=10.9 Hz, 2H), 2.84 (br s, 2H), 3.51-3.53 (m, 1H), 3.96-3.98 (m, 2H), 6.34 (d, J=7.6 Hz, 1H), 6.79 (dd, J=7.9 Hz, J=5.6 Hz, 1H), 7.95 (d, J=5.5 Hz, 1H), 8.08 (d, J=4.0 Hz, 1H). MS (ESI): 296.2 [M+H]+.

Provenance & Evidence