2,4-Dichloropyrimidine → tert-Butyl 4-((2-chloropyrimidin-4-yl)amino)piperidine-1-carboxylate

Participants

Reaction Steps

A mixture of 2,4-dichloro-pyrimidine (4.0 g, 26.85 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (6.45 g, 32.22 mmol, 1.2 equiv) in anhydrous DMF (100 mL) was stirred at rt for 18 h. The organic phase was concentrated under reduced pressure and the crude reaction mixture purified with silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 3.2 g (38%) of the title compound. 1H NMR (400 MHz, CDCl3): δ1.35-1.45 (m, 2H), 1.47 (s, 9H), 1.99-2.03 (m, 2H), 2.91-2.97 (m, 2H), 3.81-3.90 (m, 1H), 4.04-4.07 (br d, 2H), 5.33 (d, J=8.0 Hz, 1H), 6.25 (d, J=4.0 Hz, 1H), 7.98 (d, J=4.0 Hz, 1H). 13C NMR (75 MHz, DMSO): δ 28.05, 30.94, 42.04, 46.69, 78.64, 105.13, 153.86, 155.57, 159.81, 162.72. MS (ISP): 313.1 [M+H]+.

Provenance & Evidence