Reaction #2146740

Reaction equation

sodium hydroxide

NH4OH

Azithromycin

sodium acetate

CH2Cl2 MeOH NH4OH

iodine

→

compound 2

Yield 55.0%

3′-N-desmethylazithromycin

Yield 55.0%

Solvents

H2O

MeOH

Conditions

Workup

1. 1
   TemperatureThe reaction was maintained at a pH between 8 and 9
2. 2
   Other45 minute intervals
3. 3
   workup.WAITwas continued for 2 hours
4. 4
   TemperatureThe reaction was cooled to room temperature
5. 5
   Extractionextracted with CHCl3 (3×30 mL)
6. 6
   WashThe combined organic layers were washed with H2O (30 mL)
7. 7
   workup.ADDITIONcontaining NH4OH (1.5 mL)
8. 8
   Dryingdried over Na2SO4
9. 9
   Otherthe solvent evaporated
10. 10
    Otherto give a white residue
11. 11
    OtherThe crude was purified on a silica gel column
12. 12
    Washeluting with CH2Cl2/MeOH/NH4OH 18:1:0.05 to 10:1:0.05

Procedure

Azithromycin 1 (0.80 g, 1.02 mmol) and sodium acetate (NaOAc) (0.712 g, 8.06 mmol) were dissolved in 80% aqueous MeOH (25 mL). The solution was heated to 50° C. followed by addition of iodine (I2) (0.272 g, 1.07 mmol) in three batches within 3 minutes. The reaction was maintained at a pH between 8 and 9 by adding 1N sodium hydroxide (NaOH) (1 mL) at 10 min and 45 minute intervals. The solution turned colorless within 45 minutes. Stirring was continued for 2 hours. TLC(CH2Cl2/MeOH/NH4OH 10:1:0.05) after 2 hours showed a single major product (Rf=0.66). The reaction was cooled to room temperature, poured into H2O (75 mL) containing NH4OH (1.5 mL) and extracted with CHCl3 (3×30 mL). The combined organic layers were washed with H2O (30 mL) containing NH4OH (1.5 mL), dried over Na2SO4 and the solvent evaporated to give a white residue. The crude was purified on a silica gel column eluting with CH2Cl2/MeOH/NH4OH 18:1:0.05 to 10:1:0.05 to provide compound 2 (0.41 g, 55%).

Source