Reaction #52549

Reaction equation

NaOH

formic acid

9-Deoxo-9a-aza-9a-homoerythromycin A

formaldehyde

→

Azithromycin monohydrate

Solvents

acetonitrile

Conditions

Workup

1. 1
   workup.ADDITIONwere added
2. 2
   Temperaturerefluxed for 24 hours
3. 3
   Filtrationfiltered
4. 4
   Otherto remove particles
5. 5
   workup.ADDITIONTo the filtered acetonitrile solution, an equal volume of water was added
6. 6
   Otherto precipitate Azithromycin monohydrate as cube
7. 7
   FiltrationThe crystals were filtered
8. 8
   Otherdried under vacuum at 50° C.

Procedure

9-Deoxo-9a-aza-9a-homoerythromycin A (73.5 g —0.1 mole) was dissolved in 250 ml acetonitrile. To this solution, formic acid (19 ml, 0.5 mole) followed by formaldehyde (37%, 20 ml, 0.25 mole) were added and refluxed for 24 hours. The pH of the reaction mixture was adjusted with alkali (NaOH solution) to 10.5 and filtered to remove particles. To the filtered acetonitrile solution, an equal volume of water was added to precipitate Azithromycin monohydrate as cube shaped crystals. The crystals were filtered and dried under vacuum at 50° C. to give 65 g of Azithromycin monohydrate having water content of 5% (water content measured by the Karl Fischer titration method). This sample of Azithromycin monohydrate crystals has a characteristic solid state (KBr pellet) IR spectrum (FIG. 1) and a characteristic X-ray diffraction pattern (FIG. 2).

Source