Imidazole → HCID 68572249, compound

HRID 1096843Notes

Reaction equation

HRID 1096843 reaction equation
C([O:3][C:4]([C:6]1[CH:7]2[N:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:11]([CH2:12][C:13]=1[C:14]1[O:15][CH:16]=[C:17]([CH2:19][CH2:20][CH2:21][OH:22])[N:18]=1)[CH2:10][N:9]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:8]2)=[O:5])C.[OH-].[Na+].N1C=CN=C1.[CH3:45][C:46]([Si:49](Cl)([CH3:51])[CH3:50])([CH3:48])[CH3:47].[NH4+].[Cl-]>CCO.CN(C=O)C>[C:34]([O:33][C:31]([N:9]1[CH2:8][CH:7]2[N:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:11]([CH2:12][C:13]([C:14]3[O:15][CH:16]=[C:17]([CH2:19][CH2:20][CH2:21][O:22][Si:49]([C:46]([CH3:48])([CH3:47])[CH3:45])([CH3:51])[CH3:50])[N:18]=3)=[C:6]2[C:4]([OH:5])=[O:3])[CH2:10]1)=[O:32])([CH3:37])([CH3:35])[CH3:36]

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 28928tert-Butyldimethylsilyl chloride2×HCID 86637062HCID 86637062, compound

Product 1

HCID 68572249HCID 68572249, compoundYield 111.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a sol. of compound C4 (7.68 g, 14.7 mmol) in EtOH (80 mL) was added aq. 1M NaOH (80 mL). The reaction mixture was heated to 80° C. overnight. The mixture was partially concentrated under reduced pressure. The residue was acidified with aq. 3M HCl, and this aq. phase was extracted with EtOAc (5 mL). The organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. To a sol. of this crude product (6.5 g) in dry DMF (60 mL) was added imidazole (4.01 g, 58.9 mmol), and the mixture was cooled to 0° C. TBDMS-Cl (5.55 g, 36.8 mmol) was added, and the reaction mixture was stirred at rt for 2 h. Imidazole (1.5 g, 22.1 mmol) and TBDMS-Cl (2.23 g, 14.8 mmol) were added, and the mixture was stirred for 3 h. The reaction mixture was cooled to 0° C. (ice-water bath), and aq. sat. NH4Cl was slowly added. The resulting mixture was extracted with heptane/Et2O and the combined org. extracts were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was dissolved in a mixture of THF (60 mL), MeOH (20 mL) and water (20 mL). To this sol. was added K2CO3 (1.017 g). The mixture was stirred for 2 h. The mixture was concentrated under reduced pressure. The residue was dissolved in TBME, and was washed with aq. sat. NH4Cl. The aq. layer was extracted with TBME. The combined org. extracts were dried over MgSO4, filtered, and concentrated under reduced pressure. Drying the residue under high vacuum yielded the title compound (10 g, quantitative) that was used without purification. LC-MS: tR=1.12 and 1.16 min; ES+: 608.32.

Workup

  1. concentrationThe mixture was partially concentrated under reduced pressure
  2. extractionthis aq. phase was extracted with EtOAc (5 mL)
  3. dry with materialThe organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. customthe solvents were removed under reduced pressure
  6. temperaturethe mixture was cooled to 0° C
  7. stirringthe mixture was stirred for 3 h
  8. additionwas slowly added
  9. extractionThe resulting mixture was extracted with heptane/Et2O
  10. dry with materialextracts were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe crude product was dissolved in a mixture of THF (60 mL), MeOH (20 mL) and water (20 mL)
  14. additionTo this sol. was added K2CO3 (1.017 g)
  15. stirringThe mixture was stirred for 2 h
  16. concentrationThe mixture was concentrated under reduced pressure
  17. dissolutionThe residue was dissolved in TBME
  18. washwas washed with aq. sat. NH4Cl
  19. extractionThe aq. layer was extracted with TBME
  20. dry with materialextracts were dried over MgSO4
  21. filtrationfiltered
  22. concentrationconcentrated under reduced pressure
  23. customDrying the residue under high vacuum

Sources & evidence

ORD record
ord-41f1a63c3acd446083e0d63018ed15a4
Source dataset
uspto-grants-2012_03
Patent number
US08138340B2

Reaction notes

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