2-Oxazolecarboxylicacid,5-methoxy-(9CI) synthesis

Yield:439109-82-7 11%

Reaction Conditions:

Stage #1: methyl 5-methoxy-1,3-oxazole-2-carboxylatewith methanol;lithium hydroxide;water in tetrahydrofuran at 20; for 2 h;
Stage #2: with hydrogenchloride in tetrahydrofuran;ethanol; pH=4;

Steps:

50.3

3) 5-Methoxyoxazole-2-carboxylic acid Lithium hydroxide monohydrate (3.072 g) was added to a mixed solution of 5-methoxyoxazole-2-carboxylic acid methyl ester (10.26 g) in tetrahydrofuran (150 mL), methanol (75 mL), and water (75 mL) at room temperature, and the resultant mixture was stirred for 2 hours. The reaction solution was made weakly acidic (PH 4) by adding 1 M hydrochloric acid-ethanol solution, and then most of the organic solvent was evaporated under reduced pressure. Chloroform-methanol (10: 1) was added to a residue thus obtained, and the mixture was partitioned. Further, the aqueous layer was extracted with chloroform-methanol (10: 1), and the organic layers were combined and dried over anhydrous sodium sulfate. After separation by filtration, the solvent was evaporated under reduced pressure, and 5-methoxyoxazole-2-carboxylic acid [1.06 g, 11%; ¹H-NMR (400 MHz, DMSO-d₆) δ: 3.91 (3H, s), 6.45 (1H, s). EI-MSm/z: 143 (M⁺)] was obtained as a solid. The organic solvent in the aqueous layer was further evaporated under reduced pressure, and the precipitated solid was filtered, combined with the previously obtained solid, to obtain a crude product of 5-methoxy oxazol-2-carboxylic acid (15.63 g).

References:

EP1785418,2007,A1 Location in patent:Page/Page column 66