Imidazole → 2-(Methylthio)-6-{[(triisopropylsilyl)oxy]methyl}nicotinonitrile

HRID 2247749Notes

Reaction equation

HRID 2247749 reaction equation
[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[C:5]([S:11][CH3:12])[N:4]=1)=[O:2].[BH4-].[Na+].N1C=CN=C1.[CH:20]([Si:23](Cl)([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])([CH3:22])[CH3:21]>CO.C(OCC)(=O)C.CN(C)C=O.O>[CH3:12][S:11][C:5]1[N:4]=[C:3]([CH2:1][O:2][Si:23]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:20]([CH3:22])[CH3:21])[CH:10]=[CH:9][C:6]=1[C:7]#[N:8]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 139400Triisopropylsilyl chlorideHCID 27995046-Formyl-2-(methylsulfanyl)nicotinonitrileHCID 4311764Sodium borohydride

Product 1

HCID 685228342-(Methylthio)-6-{[(triisopropylsilyl)oxy]methyl}nicotinonitrileYield 91%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-formyl-2-(methylthio)nicotinonitrile (1.0 g, 5.6 mmol) in methanol (10 ml) was slowly added sodium borohydride at 0° C. with stirring, and the resulting mixture was stirred at the same temperature for 10 minutes. After evaporating the solvent in vacuo, the residue obtained was diluted with ethyl acetate, poured into water (20 ml) and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo. Subsequently, to a solution of the residue obtained and imidazole (0.76 g, 11 mmol) in N,N-dimethylformamide (6 ml) was added triisopropylsilyl chloride (1.3 ml, 6.2 mmol) with stirring, and the resulting mixture was stirred at room temperature for 2 hours. After stirring, the reaction mixture was poured into water (20 ml) and extracted with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (0:10 to 3:97) as the eluent to afford the title compound (1.7 g) in a yield of 91% as a colourless oily product.

Workup

  1. customat 0° C.
  2. stirringthe resulting mixture was stirred at the same temperature for 10 minutes
  3. customAfter evaporating the solvent in vacuo
  4. customthe residue obtained
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. filtrationAfter filtration
  9. customthe filtrate was evaporated in vacuo
  10. customSubsequently, to a solution of the residue obtained
  11. stirringwith stirring
  12. stirringthe resulting mixture was stirred at room temperature for 2 hours
  13. stirringAfter stirring
  14. extractionextracted with ether
  15. washThe extract was washed with a saturated aqueous solution of sodium chloride
  16. dry with materialdried over magnesium sulfate
  17. filtrationAfter filtration
  18. customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-37d95330a6014a68b81ad017ef82ff7d
Source dataset
uspto-grants-2010_03
Patent number
US07687491B2

Reaction notes

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