Hydrochloric Acid → Methyl 3-hydroxyisoxazole-5-carboxylate

Prepared according to Synthesis 1985, 1100. To a stirred solution of N-hydroxyurea (3.80 g, 50 mmol) and 1,5-diazabicyclo[5.4.0]undec-5-ene (8.37 g, 55 mmol) in methanol (50 mL) with cooling (ice bath) was added dimethyl ethyne dicarboxylate (7.11 g, 50 mmol) dropwise over 20 min. A dark red colour appeared then dissipated with each drop added, until finally a deep orange/red clear solution had formed. After an additional 20 min the mixture was concentrated to give a red oil which was then acidified with cooling in an ice/water bath to pH 1 with HCl (conc.). The resulting yellow mixture was extracted with diethyl ether (3×40 mL) then the aqueous phase was saturated with brine and extracted with ether (2×50 mL). The combined organic layers were then washed with water and brine and then dried over sodium sulfate, filtered and evaporated to afford the title compound (2.89 g, 40%) as white crystals after recrystallisation from chloroform. MS: m/e=143.8 [M+H]+.