2',4"-O-Bis(trimethylsilyl)erythromycin A 9-O-(1-ethoxy-1-methylethyl)oxime was synthesized in one pot and characterized. The crystal structure of the title compound grown from acetone-water was determined by the single crystal X-ray structure analysis. The crystal belongs to tetragonal system with I4 space group and a＝b＝2.9536(1) nm, c＝1.4488(1) nm, V＝12.63897(4) nm³, Z＝8, R＝0.068, wR＝0.067 for 7266 unique reflections. The research on the regioselectivity has shown that the concentration should be confined within 0.052～0.067 mol/L. Among the candidates of CH₂Cl₂-DMSO, methyl t-butyl ether-DMSO and toluene-DMSO, toluene-DMSO was the best mixture solvent for methylation with 81.69% selectivity to 6-OH, instead of the original expensive THF-DMSO.

Key words: crystal, regioselectivity, clarithromycin