Glycerol and aminophenol intermolecular condensation has been investigated through a milling and microwave-assisted sequential strategy, towards the synthesis of a benzoxaxine derivative. Mechanochemical activation prior to the microwave-assisted process could improve the probability of contact between the reagents, and greatly favors the higher conversion of aminophenol. At the same time, following a mechanochemical–microwave sequential approach could tune the selectivity towards the formation of a benzoxazine derivative, which could find application in a wide range of biomedical areas.