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

Participants

Reaction Steps

To a solution of 6.6 g (25 mmol) of triphenylphosphine in 125 mL of CH2Cl2 was added 1.7 g (25 mmol) of imidazole followed by 6.3 g (25 mmol) of iodine, and the mixture was stirred at rt for 30 min, after which 2.0 g (8.32 mmol) of 1-t-butoxycarbonyl-4-(2-hydroxyethyl) piperidine (from EXAMPLE 113, Step A) was added in CH2Cl2 and the mixture was stirred overnight at rt . The mixture was diluted with H2O, the phases were separated, and the organic phase washed with sat'd NaCl and 0.25 M Na2SO3 solution. The aqueous phase was then extracted 3× with CH2Cl2, and the combined organic layers were dried over Na2SO4, filtered and the filtrate concentrated to provide a white solid. The solid was taken up in hexane, filtered and washed with hexane. The filtrate was concentrated. Flash chomatography on 100 g of silica gel using 17:3 v/v hexanes/EtOAc as the eluant afforded 2.8 g (96%) of the title compound: 1H NMR (500 MHz) δ 1.11 (dq, J=4.4, 8.2, 2H), 1.46 (s, 2H), 1.55-1.63 (m, 1H). 1.66 (d, J=12.6, 2H), 1.78 (q, J=7.1, 2H), 2.65-2.75 (2H), 5.22 (2H), 3.22 (t, J=7.1, 2H), 4.1 14.15 (5H).

Provenance & Evidence