4-Chlorophenol → 7-[1-(4-Chlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine

Participants

Reaction Steps

A solution of diisopropyl azodicarboxylate (11 g, 1.1 eq) in toluene (20 ml) was added dropwise to a stirred mixture of 1-(1,2,4-triazolo[1,5-a]pyrimidin-7-yl)ethanol (8.1 g, recrystallised from tetrahydrofuran, 49 mmol), 4-chlorophenol (6.35 g, 1 eg), triphenylphosphine (12.95 g, 1 eq) and toluene (200 ml) under nitrogen at 0-5° C. and the mixture then stirred at ambient temperature overnight. Magnesium chloride (9.5 g, -˜2 eq) was added and the stirred mixture heated under reflux for 1.5 hours, cooled to −5° C. and filtered, washing the filter pad with further toluene (2×50 ml). ml). The combined filtrate was washed with water (2×200 ml), sodium hydroxide solution (1M, 2×50 ml), and then water (2×50 ml) and then the solvent evaporated. Propan-2-ol (50 ml) was added to the residue and the solvent evaporated; this was repeated. The residue was dissolved in propan-2-ol (50 ml), seeded with a crystal of product, and left to stand at 0-5° C. for 72 hours. The product was collected by filtration, washed with cold propan-2-ol (2×20 ml) and dried in vacuo to yield 7-[1-(4-chlorophenoxy)ethyl]1,2,4-triazolo[1,5-a]pyrimidine (7.1 g, 53%), which was analysed for triphenylphosphine oxide content.

Provenance & Evidence