Imidazole → Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Combined 4-(2-hydroxy-1-ethyl)-1-tert-butoxycarbonyl-piperidine (37.4 g, 0.16 mol, from Step B), triphenylphosphine (55 g, 0.21 mol) and imidazole (14 g, 0.21 mol) in 800 mL of 33% acetonitrile in ether. Cooled to 0° C. and added iodine (56 g, 0.22 mol) portionwise. Diluted with 1 L of ether. Washed organic layer with 2×500 mL each of sat. aq. Na2S2O3, sat. aq. CuSO4 and brine. Dried over MgSO4, filtered and concentrated. Triphenylphosphine oxide precipitates. Added ether and filtered the slurry through a plug of silica gel. Purified a portion of the crude material by flash chromatography (5% ethyl acetate in hexane eluent) to afford the title compound. 1H-NMR (400 Mhz, CDCl3): δ 4.10 (br s, 2H), 3.23 (t, 2H, J=7.2 Hz), 2.72 (br t, 2H, 12.3 Hz), 1.79 (q, 2H, J=7 Hz), 1.67 (br d, 2H, 14 Hz), 1.61 (m, 1H), 1.47 (s, 9H), 1.14 (qd, 2H, J=4.3, 12 Hz); ESI-MS: 340 (M+H); HPLC A: 3.74 min.

Provenance & Evidence