Tetrahydrofuran → 1-Isobutyl-2-amino-6-formylbenzimidazole

HRID 250747Notes

Reaction equation

HRID 250747 reaction equation
C1([Li])C=CC=CC=1.[CH2:8]([N:12]1[C:16]2[CH:17]=[C:18](Br)[CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[NH2:22])[CH:9]([CH3:11])[CH3:10].C([Li])(C)(C)C.[Cl-].[NH4+].[O:30]1CCC[CH2:31]1>CN(C)C=O>[CH2:8]([N:12]1[C:16]2[CH:17]=[C:18]([CH:31]=[O:30])[CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[NH2:22])[CH:9]([CH3:11])[CH3:10]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 653467761-Isobutyl-2-amino-6-bromobenzimidazoleHCID 178418306HCID 178418306, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 860671521-Isobutyl-2-amino-6-formylbenzimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add phenyllithium (19.4 mL, 33 mmol, 1.7M in cyclohexane/diethyl ether) dropwise over 20 minutes to a solution of 1-isobutyl-2-amino-6-bromobenzimidazole (2.68 g, 10 mmol) in tetrahydrofuran (50 mL) at −78° C. Stir 40 minutes after addition is complete and then add tert-butyllithium (17.6 mL, 30 mmol, 1.7M in pentane) dropwise over 20 minutes. Stir 1.5 hours after addition is complete and then add dimethylformamide (5 mL) dropwise over 5 minutes. Warm reaction mixture to 0° C. over 1 hour, and then to room temperature over 20 minutes. Dilute reaction mixture with saturated aqueous ammonium chloride (100 mL), and then extract well with ethyl acetate. Combine ethyl acetate extracts, wash sequentially with water and saturated aqueous sodium chloride, dry over sodium sulfate and concentrate under reduced pressure. Slurry the residue in diethyl ether, filter and dry to provide 1.58 g of the title compound.

Workup

  1. additionafter addition
  2. stirringStir 1.5 hours
  3. additionafter addition
  4. temperatureWarm
  5. customreaction mixture to 0° C. over 1 hour
  6. waitto room temperature over 20 minutes
  7. additionDilute
  8. extractionextract well with ethyl acetate
  9. washwash sequentially with water and saturated aqueous sodium chloride
  10. dry with materialdry over sodium sulfate
  11. concentrationconcentrate under reduced pressure
  12. filtrationfilter
  13. customdry

Sources & evidence

ORD record
ord-0bae218967c648849baefcba5f547eb8
Source dataset
uspto-grants-2011_01
Patent number
US07863310B2

Reaction notes

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