Acetic Anhydride → Erythromycin 2'-acetate

Participants

Reaction Steps

Erythromycin A (50.0 g, 68.1 mmol) (commercially available from Abbott Laboratories) was dissolved in 600 mL of methylene chloride (CH2Cl2) at ambient temperature. Triethylamine (20 mL) and 10 mL (10.82 g, 106 mmol) of acetic anhydride were added to this solution. The reaction mixture was heated to reflux and 100 mL of CH2Cl2 was distilled from the reaction mixture to remove any traces of water. The reaction mixture was heated at reflux temperature for an additional five hours. After six hours, when the reaction was complete, according to TLC analysis, the reaction mixture was cooled to ambient temperature and transferred to a separatory funnel. The CH2Cl2 solution was washed with 300 mL of ammonium hydroxide/sodium bicarbonate solution containing 2.9% ammonia and 1.8% sodium bicarbonate, dried over anhydrous sodium sulfate and filtered. The CH2Cl2 was removed using a rotary evaporator with a water bath temperature of 30°-40° C. The residue was crystallized from 200 mL of acetonitrile (CH3CN) by first dissolving it in hot CH3CN and allowing the solution to stand overnight at ambient temperature, then cooling it to -25° C. and maintaining this temperature for 24 hours. The product was isolated as white crystals which were washed with cold (-25° C.) CH3CN and dried in a vacuum oven at 50° C. for approximately 64 hours. The 2'-O-acetylerythromycin A was obtained in 83% yield (43.91 g).

Provenance & Evidence