Oxazole-4-carbaldehyde

155742-48-6

118994-84-6

The general procedure for the synthesis of oxazole-4-carbaldehyde from 4-oxazolemethanol was as follows: a solution of anhydrous dichloromethane (200 mL) with dimethylsulfoxide (DMSO, 19.3 mL, 272 mmol) was added slowly and dropwise to a solution of anhydrous dichloromethane (200 mL) with oxalyl chloride (17.3 mL, 204 mmol) at -63 °C. The reaction mixture was stirred at -63 °C for 15 min before adding an anhydrous dichloromethane (200 mL) solution of 4-oxazole methanol (13.5 g, 204 mmol) with a controlled dropwise addition time of 15 min. Stirring was continued at -63 °C for 60 min, followed by the addition of triethylamine (Et3N, 53.1 mL, 381 mmol). The reaction mixture was gradually warmed up to room temperature. Upon completion of the reaction, the mixture was combined with 10% aqueous citric acid solution and extracted with dichloromethane (4 times) and ethyl acetate (2 times). The organic phases were combined, washed with a small amount of saturated aqueous sodium bicarbonate solution and extracted again with dichloromethane (3 times) and ethyl acetate (3 times). All organic phases were combined, dried with magnesium sulfate (MgSO4), filtered and the solvent was removed under reduced pressure. The residue was purified by column chromatography (eluent: ether/petroleum ether, ratio tapered from 1:1 to 2:1, to 4:1 and finally 1:0) to give oxazole-4-carbaldehyde (11.9 g, 86% yield). Thin layer chromatography (TLC) showed an Rf value of 0.65 (Expander: methanol/dichloromethane, 1:9).