Robinson–Gabriel synthesis

The reaction requires trifluoroacetic anhydride to be used as the cyclodehydrating agent in ethereal solvent and the 2-acylamidoketone be linked by the nitrogen atom to a benzhydrylic-type linker.

[7] A popular extension of the Robinson-Gabriel cyclodehydration has been reported by Wipf et al. to allow the synthesis of substituted oxazoles from readily available amino acid derivatives.

[10] Oxazoles have been found to be common substructures in multiple naturally isolated compounds and have thus garnered attention within the chemical and pharmaceutical community.

[15] Eric Biron et al. developed a solid-phase synthesis of 1,3-oxazole-based peptides on solid phase from dipeptides by oxidation of the side-chain followed by Wipf and Miller's cyclodehydration of β-ketoamides described above.

Starting with aspartic acid β esters undergoing acylation to differentiate the first substituent, linked to carbon-2, followed by Dakin-West conversion to keto-amide to introduce the second substituent, and ending with the Robinson-Gabriel cyclodehydration at 90°C for 30 minutes with either phosphorus oxychloride in dimethylformamide or catalytic sulfuric acid in acetic anhydride.