The title erythromycin O-(phenoxypropyl)oxime was prepared by alkylation of the known erythromycin A 9-oxime (I) with 3-phenoxypropyl bromide (II) under phase-transfer conditions in the presence of KOH and tetrabutylammonium iodide in THF.
The reaction of erythromycin A (I) with hydroxylamine in pyridine gives the corresponding oxime (II), which is alkylated with 3-cyclohexylpropyl bromide (III), KOH and tetrabutylammonium iodide in THF to yield the O-alkylated oxime (IV). The reaction of (IV) with Ac2O in pyridine affords the diacetoxyerythromycin A (V), which is finally selectively monodeacetylated in methanol at room temperature to provide the target 4''-O-acetyl derivative.