The invention belongs to the technical field of chemistry, and in particular relates to a method for synthesizing azithromycin rearrangement impurity lactam. Its main steps are: (3R,4R,5S,6R,9R,10S,11S,12R,13R,15R,Z)‑12‑[[3,4,6‑trideoxy‑3‑(dimethylamino)‑ β-D-wood-hexyranosyl]oxy]-6-ethyl-4,5-dihydroxy-10-[(2,6-dideoxy-3-C-methyl-3-O-methyl yl-a-L-nucleo-hexyranosyl)oxy]-3,5,9,11,13,15-hexamethyl-7,16-dioxo-2-azabicyclo[11.2.1] Hexadecane-1-en-8-one (compound Ⅱ) undergoes acidification and alkalinization rearrangement, and after purification, the rearranged impurity lactam with a purity >99.5% is obtained. The synthesized high-purity azithromycin rearrangement impurity lactam is used as the impurity standard for finished product detection, which is conducive to strengthening the positioning and characterization of the impurity and improving the quality control of azithromycin API.