Cyclohexanecarboxylic acid → Methyl 5-cyclohexyl-1,3-oxazole-4-carboxylate

Participants

Reaction Steps

To an ice-cold mixture of cyclohexanecarboxylic acid (5.40 g, 42.1 mmol) and K2CO3 (23.3 g, 168.4 mmol) in N,N-dimethylformamide (60 mL) were added diphenylphosphoryl azide (16.1 g, 58.5 mmol) and methyl isocyanoacetate (5.0 g, 50.5 mmol). After being stirred at room temperature for 16 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated NaHCO3 solution, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting light yellow solid was recrystallized from hexane-ethyl acetate to give the title compound (4.47 g, 51%) as an off-white solid. The mother liquid was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 90:10 to 30:70) to give a light yellow solid. This solid was triturated with hexane-diisopropyl ether to give the title compound (2.05 g, 23%) as a light yellow solid.

Provenance & Evidence