Dichloromethane → Flurithromycin

Participants

Reaction Steps

Erythromycin A (5 g, 6.813 mmole) was dissolved in glacial acetic acid (20 mL) at room temperature and stirred for 2 hours. The pH of the mixture was adjusted to 4.3 with 6N sodium hydroxide (approx. 12.5 mL) while the temperature was maintained below 20° C. N-fluorobenzenesulfonimide (2.2 g, 6.813 mmole) was added and stirring continued for an additional 18 hours at 22° C. Methylene chloride (100 mL) was added, the solution was placed in an ice bath while the pH of the mixture was adjusted to 9 with 6N sodium hydroxide (approx. 85 mL) and the temperature was maintained below 20° C. Next, water (100 mL) was added, the layers separated and the aqueous layer washed an additional two times with methylene chloride (100 mL each). The methylene chloride serves as an extractant for the flurithromycin product. The combined organic phases were washed 2 to 4 times with 5 percent sodium hydroxide (100 mL each) and dried over magnesium sulfate. After filtration, the organic phase was concentrated under vacuum at room temperature to afford 4.91 g of crude flurithromycin. The crude material was dissolved in ethanol concentrated to 20 mL. This process was repeated two more times. After standing at 0° C. for one night, the product was filtered under vacuum, washed with 5 mL cold ethanol and dried under vacuum at 40° C. to afford 3.48 g (68% yield) of flurithromycin ((8S)-8-fluoroerythromycin).

Provenance & Evidence