Reaction #164457

Reaction equation

sodium hydroxide

NH4OH

Azithromycin

sodium acetate

iodine

→

amine

Yield 55.0%

3′-N-desmethylazithromycin

Yield 55.0%

Solvents

H2O

methanol

Conditions

Workup

1. 1
   TemperatureThe reaction was maintained at a pH between 8-9
2. 2
   Other45 minute intervals
3. 3
   workup.WAITwas continued for 2 hours
4. 4
   Other(hr)
5. 5
   TemperatureThe reaction was cooled to room temperature (rt)
6. 6
   Extractionextracted with chloroform (CHCl3) (3×30 mL)
7. 7
   WashThe combined organic layers were washed with H2O (30 mL)
8. 8
   workup.ADDITIONcontaining NH4OH (1.5 mL)
9. 9
   Dryingdried over Na2SO4
10. 10
    Otherthe solvent evaporated
11. 11
    Otherto give a white residue
12. 12
    OtherThe crude was purified on a silica gel column
13. 13
    Washeluting with CH2Cl2/MeOH/NH4OH 18:1:0.05 to 10:1:0.05

Procedure

Azithromycin 1 (0.80 grams (g), 1.02 millimoles (mmol)) and sodium acetate (NaOAc) (0.712 g, 8.06 mmol) were dissolved in 80% aqueous methanol (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 8-9 by adding 1N sodium hydroxide (NaOH) (1 mL) at 10 min and 45 minute intervals. The solution turned colorless within 45 minutes (min), however, stirring was continued for 2 hours (hr). TLC methylene chloride(CH2Cl2)/MeOH/ammonium chloride (NH4OH) 10:1:0.05) after 2 hours showed a single major product (Rf=0.66). The reaction was cooled to room temperature (rt), poured into H2O (75 mL) containing NH4OH (1.5 mL) and extracted with chloroform (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 amine 2 (0.41 g, 55%).

Source