Dichloromethane → Flurithromycin

Participants

Reaction Steps

Anhydroerythromycin A (1 g, 1.4 mmole) was dissolved in glacial acetic acid (4-mL) at room temperature and the pH of the mixture was adjusted to 4.3 with 6N sodium hydroxide (approx. 2.5 mL) while the temperature was maintained below 20° C. N-fluorobenzenesulfonimide (0.44 g, 1.4 mmole) was added and stirring continued for an additional 18 hours at 22° C. Methylene chloride (10 mL) was added, the solution placed in an ice bath while the pH of the mixture was adjusted to 9 with 6N sodium hydroxide (approx. 17 mL) and the temperature maintained below 20° C. Next, water (10 mL) was added, the layers separated and the aqueous layer washed an additional two times with methylene chloride (10 mL each). The combined organic phases were washed 2 to 4 times with 5% sodium hydroxide (10 mL each) and dried over magnesium sulfate. After filtration, the organic phase was concentrated under vacuum at room temperature to afford 0.88 g of crude flurithromycin. The crude material was dissolved in ethanol concentrated to 2 mL. This process was repeated two more times. After standing at 0° C. for one night, the product was filtered under vacuum, washed with 0.5 mL cold ethanol and dried under vacuum at 40° C. to afford 0.53 g (51% yield) of flurithromycin.

Provenance & Evidence