Reaction of p-aminobenzoic acid methyl ester (I) with methanesulfonyl chloride using pyridine as base provides the methanesulfonyl derivative (II). Heating (II) in heat N,N-diethyl-1,2-ethanediamine (III) at 140-50 C until complete disappearance of (II) gives the crude sematilide, which, after removal of excess diamine under vacuum, is crystallized as the hydrochloride salt from isopropanol/aqueous HCl.