4-Amino-1-Boc-piperidine → HCID 67196123, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 4-bromo-2-methyl-pyridine (1.99 g, 11.55 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.78 g, 13.86 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (3.24 g, 28.87 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.11 g, 0.23 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone) dipalladium(0) (0.96 g, 0.92 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 ethyl acetate/triethylamine (10:0→9:1) to provide 1.75 g (52%) of the title compound in 90% purity according to 1H NMR. 1H NMR (400 MHz, DMSO): δ 1.14-1.29 (m, 2H), 1.40 (s, 9H), 1.84 (d, J=12.8 Hz, 2H), 2.24 (s, 3H), 2.90 (br s, 2H), 3.40-3.53 (m, 1H), 3.86 (d, J=13.0 Hz, 2H), 6.23-6.33 (m, 2H), 6.35 (s, 1H), 7.87 (d, J=5.8 Hz, 1H). MS (ESI): 292.2 [M+H]+.

Provenance & Evidence