4-Bromophenol → 4-(4-Bromophenoxymethyl)piperidine-1-carboxylic acid isopropyl ester

Participants

Reaction Steps

Diisopropyl azodicarboxylate (9.1 mL, 46.27 mmol) in THF (15 mL) was added dropwise to a solution of 1-methylethyl 4-(hydroxymethyl)-1-piperidinecarboxylate (7.76 g, 38.56 mmol), 4-bromophenol (6.67 g, 38.56 mmol) and Ph3P (13.15 g, 50.12 mmol) in THF (85 mL) at −20° C. The reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature overnight. The mixture was concentrated, and the residue was purified by chromatography on a silica gel column using 0 to 25% EtOAc/hexane to give the crude product. The crude product was taken up in Et2O (250 mL) and washed with 1N NaOH (aq). The organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated to give 7.5 g (55%) of 1-methylethyl 4-{[(4-bromophenyl)oxy]methyl}-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ7.35 (d, 2H, J=8.9 Hz), 6.75 (d, 2H, J=8.9 Hz), 4.96-4.83 (m, 1H), 4.24-4.14 (m, 2H), 3.75 (d, 2H, J=6.4 Hz), 2.81-2.71 (m, 2H), 2.02-1.87 (m, 1H), 1.85-1.75 (m, 2H), 1.33-1.13 (m, 8H); LRMS (ESI), m/z 356/358 (M+H).

Provenance & Evidence