Imidazole → 1-Benzyl-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)piperidin-4-one

HRID 2265146Notes

Reaction equation

HRID 2265146 reaction equation
N1C=CN=C1.[C:6]([Si:10]([CH3:13])([CH3:12])Cl)([CH3:9])([CH3:8])[CH3:7].CN(C)C=O.[CH2:19]([N:26]1[CH2:31][CH2:30][C:29]([OH:32])=[C:28]([C:33](OC)=[O:34])[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(OCC)(=O)C.CO>[CH2:19]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH:28]([CH2:33][O:34][Si:10]([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:13])[CH3:12])[CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 54682501Methyl 1-benzyl-1,2,5,6-tetrahydro-4-hydroxynicotinate

Product 1

HCID 224957221-Benzyl-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)piperidin-4-oneYield 42%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.82 g of imidazole and 0.72 g of tert-butyldimethylchlorosilane were added to N,N-dimethylformamide (10 mL) solution of 1.0 g of methyl 1-benzyl-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylate, and stirred at room temperature for 0.5 hours, and then methanol was added thereto. The reaction solution was diluted with ethyl acetate, washed with water and saturated saline water in that order, dried with anhydrous sodium sulfate, and the solvent was evaporated off under reduced pressure. The resulting residue was dissolved in 30 mL of diethyl ether, and with cooling with ice, 0.30 g of lithiumaluminium hydride was added thereto, and stirred at that temperature for 1.5 hours, and then methanol was added thereto. The reaction solution was diluted with ethyl acetate, then washed with water and saturated saline water in that order, dried with anhydrous sodium sulfate, and the solvent was evaporated off under reduced pressure. High-polarity side products were removed from the resulting residue through silica gel column chromatography (chloroform/methanol=10/1), and the residue was dissolved in 10 mL of N,N-dimethylformamide, and 0.41 g of imidazole and 0.72 g of tert-butyldimethylchlorosilane were added thereto, and stirred at room temperature for 10 minutes. Water was added to the reaction solution, and diluted with ethyl acetate. Then, this was washed with water and saturated saline water in that order, dried with anhydrous sodium sulfate, and the solvent was evaporated off under reduced pressure. The residue was separated and purified through silica gel column chromatography (hexane/ethyl acetate=10/1 to 4/1) to obtain 566 mg of the entitled compound as a pale yellow oily substance.

Workup

  1. washwashed with water and saturated saline water in that order
  2. dry with materialdried with anhydrous sodium sulfate
  3. customthe solvent was evaporated off under reduced pressure
  4. dissolutionThe resulting residue was dissolved in 30 mL of diethyl ether
  5. temperaturewith cooling with ice, 0.30 g of lithiumaluminium hydride
  6. additionwas added
  7. stirringstirred at that temperature for 1.5 hours
  8. additionmethanol was added
  9. additionThe reaction solution was diluted with ethyl acetate
  10. washwashed with water and saturated saline water in that order
  11. dry with materialdried with anhydrous sodium sulfate
  12. customthe solvent was evaporated off under reduced pressure
  13. customHigh-polarity side products were removed from the resulting residue through silica gel column chromatography (chloroform/methanol=10/1)
  14. dissolutionthe residue was dissolved in 10 mL of N,N-dimethylformamide
  15. addition0.41 g of imidazole and 0.72 g of tert-butyldimethylchlorosilane were added
  16. stirringstirred at room temperature for 10 minutes
  17. additionWater was added to the reaction solution
  18. additiondiluted with ethyl acetate
  19. washThen, this was washed with water and saturated saline water in that order
  20. dry with materialdried with anhydrous sodium sulfate
  21. customthe solvent was evaporated off under reduced pressure
  22. customThe residue was separated
  23. custompurified through silica gel column chromatography (hexane/ethyl acetate=10/1 to 4/1)

Sources & evidence

ORD record
ord-1bf1aab734de4694acd78769a7f360fe
Source dataset
uspto-grants-2010_12
Patent number
US07855294B2

Reaction notes

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