Acetylsalicylic acid (I) was converted to acid chloride (II) by refluxing in a SOCl2 solution. Condensation of acid chloride (II) with guaiacol (III) either in the absence or in the presence of tertiary amines gave rise to the target orthoester derivative. Alternatively, the title compound has been prepared by treatment of acetylsalicylic acid (I) with several acid anhydrides, followed by guaiacol (III).