Exploring the amide coupling of carboxylic acids with amines using green solvent limonene

Limonene was identified as green media for amide formation through quantum chemistry calculation. An environmentally benign and sustainable protocol for amide formation was developed with simple filtration without the need for extensive isolation and purification. Additionally, the scope and general compatibility of the proposed method were explored with aromatic and aliphatic substrates, giving moderate to excellent yields, and a gram-scale synthesis of SHP1 activator 3a-18 were easily performed for further biological evaluation.