3-Fluorophenol → Tert-butyl 4-(3-fluorophenoxy)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl 4-hydroxy-1-piperidinecarboxylate (24 g, 112 mmol), 3-fluorophenol (5.6 g, 59 mmol) and triphenylphosphine (31.4 g, 118 mmol) in THF (100 ml) was added di-isopropylazodicarboxylate (23.3 ml, 118 mmol). The reaction was stirred at room temperature over-weekend and then the solvent was removed in vacuo. The residue was diluted with DCM, hexane was added and the resultant precipitate was filtered off. The filtrate was concentrated in vacuo and purified by column chromatography. Elution with DCM gave the title compound (16.4 g, 87% pure). δH (CDCl3, 250 MHz) 1.47 (9H, s), 1.76 (2H, m), 1.92 (2H, m), 3.35 (2H, ddd), 3.69 (2H, ddd), 4.44 (1H, m), 6.65 (3H, m), 7.20 (1H, m).

Provenance & Evidence