Imidazole → (S)-3-[tert-butyldimethylsilyloxy]glutaric acid monoamide

HRID 921500Notes

Reaction equation

HRID 921500 reaction equation
C([O:8][C:9](=[O:17])[CH2:10][C@@H:11]([OH:16])[CH2:12][C:13]([NH2:15])=[O:14])C1C=CC=CC=1.N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C)C=O.ClCCl.CCCCCCC>[Si:23]([O:16][C@H:11]([CH2:10][C:9]([OH:8])=[O:17])[CH2:12][C:13]([NH2:15])=[O:14])([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]

Participants

7

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 89601064(S)-Benzyl-3-hydroxyglutaramate

Product 1

HCID 124674414(S)-3-[tert-butyldimethylsilyloxy]glutaric acid monoamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8900HeptaneSolvent

Conditions

Temperature
5 °C

Procedure

(S)-Benzyl-3-hydroxyglutaramate (100 g) was dissolved in dimethyl formamide. To this Imidazole (35 g) was added and the solution was cooled to 5° C. To this a solution of tert-butyldimethylsilylchloride (68.5 g) dissolved in dimethyl formamide (250 ml) was added under cooling. The mixture was warmed to 20-25° C. and stirred. The reaction mixture was cooled and quenched with water. To the reaction mixture ethyl acetate and water was added and stirred. The layers were separated and the organic phase was washed thrice with water. To the organic phase Palladium on charcoal (5%, 1 g) was added and stirred under hydrogen atmosphere (˜2.8 Kg). Palladium was removed by filtration. The filtrate was mixed with water and adjusted pH to ˜9.0 by using Aq ammonia solution. The reaction mass was stirred and layers were separated. The aqueous phase was washed with dichloromethane and dichloromethane was added to aqueous phase. The reaction mass was cooled to 5° C. and pH was adjusted to 4.0 with Aq phosphoric acid. The reaction mass was stirred and layers were separated. The organic phase was washed with water and dried over sodium sulphate. The organic layer was evaporated under vacuum to yield residue. Residue was dissolved in dichloromethane and to this solution heptane was added, stirred, filtered and dried to yield (S)-3-(tert-butyl dimethylsilyloxy)glutaric acid monoamide.

Workup

  1. additionwas added
  2. temperatureunder cooling
  3. temperatureThe mixture was warmed to 20-25° C.
  4. temperatureThe reaction mixture was cooled
  5. customquenched with water
  6. additionTo the reaction mixture ethyl acetate and water was added
  7. stirringstirred
  8. customThe layers were separated
  9. washthe organic phase was washed thrice with water
  10. additionTo the organic phase Palladium on charcoal (5%, 1 g) was added
  11. stirringstirred under hydrogen atmosphere (˜2.8 Kg)
  12. customPalladium was removed by filtration
  13. additionThe filtrate was mixed with water and adjusted pH to ˜9.0
  14. stirringThe reaction mass was stirred
  15. customlayers were separated
  16. washThe aqueous phase was washed with dichloromethane and dichloromethane
  17. additionwas added to aqueous phase
  18. temperatureThe reaction mass was cooled to 5° C.
  19. stirringThe reaction mass was stirred
  20. customlayers were separated
  21. washThe organic phase was washed with water
  22. dry with materialdried over sodium sulphate
  23. customThe organic layer was evaporated under vacuum
  24. customto yield residue
  25. additionwas added
  26. stirringstirred
  27. filtrationfiltered
  28. customdried

Sources & evidence

ORD record
ord-11b7d1ae205d4d72b8155d1245927214
Source dataset
uspto-grants-2016_03
Patent number
US09273333B2

Reaction notes

Loading…