Imidazole → 4-(2-Iodoethyl)-1-[2-methyl-5-(methyloxy)-4-nitrophenyl]piperidine

Participants

Reaction Steps

To 2-{1-[2-methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}ethanol (32.6 g, 111 mmol), triphenylphosphine (32.0 g, 122 mmol), and imidazole (8.29 g, 122 mmol) in THF (554 mL) was added iodine (30.9 g, 122 mmol) in one portion, slowly due to observable exotherm. The reaction mixture was filtered through Celite® and washed with DCM. Purification by flash chromatography provided the crude title compound which was washed with saturated Na2SO3 to remove any residual iodine. The aqueous layer was back extracted with DCM. The combined organic layers were dried (MgSO4), filtered, and rotovapped down to give the title compound of step G (40.6 g, 100 mmol, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J=0.5 Hz, 1H), 6.68 (s, 1H), 3.89 (s, 3H), 3.33 (t, J=7.5 Hz, 2H), 3.26 (d, J=12.4 Hz, 2H), 2.63-2.74 (m, 2H), 2.17 (s, 3H), 1.78 (q, J=7.1 Hz, 4H), 1.46-1.61 (m, J=7.2, 7.2, 7.1, 3.8 Hz, 1H), 1.30 (qd, J=12.0, 3.6 Hz, 2H).

Provenance & Evidence