The C-9 amino group of erythromycylamine (I) was protected by reaction with Boc2O to give the corresponding tert-butyl carbamate (II). Subsequent acetylation of the 2'-hydroxyl group of (II) with Ac2O provided acetate (III). Then, condensation of (III) with carbonyldiimidazole at the 4''-hydroxyl group afforded the acyl imidazole (IV). The chiral diamine (VIII) was synthesized by reductive condensation of 2-phthalimido acetaldehyde (V) with the (S)-phenylethylamine derivative (VI), followed by hydrazinolysis of the resulting phtalimide (VII). Diamine (VIII) was then coupled with acyl imidazole (IV) to afford carbamate (IX).

Introduction of an N-ethyl group in (IX) was accomplished by reductive condensation with acetaldehyde and NaBH(OAc)3 to give (X). The Boc group of (X) was deprotected by treatment with trimethylsilyl triflate and 2,6-lutidine, and then reaction of the resulting silyl ether with tetrabutylammonium fluoride in THF yielding (XI). Finally, the 2'-acetyl group of (XI) was removed by treatment with methanol.