Dimethylformamide → 3-Aminorifamycin S

HRID 1855933Notes

Reaction equation

HRID 1855933 reaction equation
[CH3:1][C@@H:2]1[C@H:37]([OH:38])[C@@H:36]([CH3:39])[C@@H:35]([OH:40])[C@@H:34]([CH3:41])[C@H:33]([O:42][C:43]([CH3:45])=[O:44])[C@H:32]([CH3:46])[C@@H:31]([O:47][CH3:48])[CH:30]=[CH:29][O:28][C@:25]2([CH3:49])[C:26](=[O:27])[C:15]3[C:16]([O:24]2)=[C:17]([CH3:23])[C:18]([OH:22])=[C:19]2[C:20](=[O:21])[C:10](=[C:11](Br)[C:12]([C:14]=32)=[O:13])[NH:9][C:7](=[O:8])[C:6]([CH3:51])=[CH:5][CH:4]=[CH:3]1.C[N:53](C)C=O>>[CH3:1][C@@H:2]1[C@H:37]([OH:38])[C@@H:36]([CH3:39])[C@@H:35]([OH:40])[C@@H:34]([CH3:41])[C@H:33]([O:42][C:43]([CH3:45])=[O:44])[C@H:32]([CH3:46])[C@@H:31]([O:47][CH3:48])[CH:30]=[CH:29][O:28][C@:25]2([CH3:49])[C:26](=[O:27])[C:15]3[C:16]([O:24]2)=[C:17]([CH3:23])[C:18]([OH:22])=[C:19]2[C:20](=[O:21])[C:10](=[C:11]([NH2:53])[C:12]([C:14]=32)=[O:13])[NH:9][C:7](=[O:8])[C:6]([CH3:51])=[CH:5][CH:4]=[CH:3]1

Participants

3

Reactant 2

HCID 6228DimethylformamideHCID 128896153-Bromorifamycin S

Product 1

HCID 128896223-Aminorifamycin S

Conditions

Temperature
20 °C

Procedure

540 g of 3-bromo-rifamycin S are dissolved in 1500 ml of N,N-dimethyl formamide at 20° C. A steam of N2 is bubbled through the solution for 20', then 60 g of sodium nitrite are added portionwise allowing the temperature to rise to 39° C. while stirring under nitrogen atmosphere. The temperature is kept at 40° C. with a water bath for 30', then cooled at 20° C.; 10 g of urea are added and 70 ml of acetic acid are added dropwise. The steam of N2 is stopped and 130 g of zinc powder are added portionwise with vigorous stirring and cooling with an ice bath to keep the temperature below 60° C. The reaction mixture is stirred allowing the temperature to decrease to room temperature, and stirring is continued for 5 hours. The reaction mixture is filtered and the solution is diluted with 3000 ml of dichloromethane and washed with water several times. The dichloromethane solution is treated with manganese dioxide in order to oxidize 3-amino-rifamycin SV to 3-amino-rifamycin S. After filtration and evaporation to dryness, raw material such obtained is crystallized from 600 ml of 2-methoxy-ethanol to give 440 g of TLC pure 3-amino-rifamycin S in black crystals. U.V.; I.R. and PMR are identical to an authenic sample prepared according to W. Kump, H. Bickel, Helv. Chem. Acta, 56(7), 2348 (1973).

Workup

  1. customA steam of N2 is bubbled through the solution for 20', then 60 g of sodium nitrite
  2. additionare added portionwise
  3. customto rise to 39° C.
  4. customThe temperature is kept at 40° C. with a water bath for 30
  5. addition10 g of urea are added
  6. addition70 ml of acetic acid are added dropwise
  7. addition130 g of zinc powder are added portionwise
  8. stirringwith vigorous stirring
  9. temperaturecooling with an ice bath
  10. customthe temperature below 60° C
  11. stirringThe reaction mixture is stirred
  12. customto decrease to room temperature
  13. stirringstirring
  14. filtrationThe reaction mixture is filtered
  15. additionthe solution is diluted with 3000 ml of dichloromethane
  16. washwashed with water several times
  17. additionThe dichloromethane solution is treated with manganese dioxide in order
  18. filtrationAfter filtration and evaporation to dryness, raw material
  19. customsuch obtained
  20. customis crystallized from 600 ml of 2-methoxy-ethanol

Sources & evidence

ORD record
ord-07c6f598d5e841b3be3ddad3b9279bb2
Source dataset
uspto-grants-1980_08
Patent number
US04217277

Reaction notes

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