Iodine → N'-(Desmethyl)azithromycin

HRID 77275

Reaktionsgleichung

Reaktionsgleichung von HRID 77275
[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41](C)[CH3:42])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[CH2:8][N:7]([CH3:48])[C@H:6]([CH3:49])[C@@H:5]([OH:50])[C@@:4]1([OH:52])[CH3:51].C([O-])(=O)C.[Na+].II.[OH-].[Na+].[NH4+].[OH-]>CO.O>[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([NH:41][CH3:42])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[CH2:8][N:7]([CH3:48])[C@H:6]([CH3:49])[C@@H:5]([OH:50])[C@@:4]1([OH:52])[CH3:51]

Komponenten

8

Edukt 5

HCID 807IodineHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 447043AzithromycinHCID 517045Sodium Acetate

Produkt 1

HCID 9987533N'-(Desmethyl)azithromycinAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

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%).

Aufarbeitung

  1. temperatureThe reaction was maintained at a pH between 8-9
  2. custom45 minute intervals
  3. waitwas continued for 2 hours
  4. custom(hr)
  5. temperatureThe reaction was cooled to room temperature (rt)
  6. extractionextracted with chloroform (CHCl3) (3×30 mL)
  7. washThe combined organic layers were washed with H2O (30 mL)
  8. additioncontaining NH4OH (1.5 mL)
  9. dry with materialdried over Na2SO4
  10. customthe solvent evaporated
  11. customto give a white residue
  12. customThe crude was purified on a silica gel column
  13. washeluting with CH2Cl2/MeOH/NH4OH 18:1:0.05 to 10:1:0.05

Quellen und Nachweise

ORD-Eintrag
ord-951783dbb6714d5d88f6e5d7fce8f46a
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841263B2

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