Sodium hydride → [6-({[tert-Butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]methanol

HRID 473221

Reaction equation

HRID 473221 reaction equation
[H-].[Na+].[N:3]1[C:8]([CH2:9][OH:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:11][OH:12].[C:13]([Si:17]([CH3:20])([CH3:19])Cl)([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C>[Si:17]([O:12][CH2:11][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([CH2:9][OH:10])[N:3]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 709572,6-Pyridinedimethanol

Product 1

HCID 14953579[6-({[tert-Butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]methanolYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 60% NaH (1.45 g, 35.9 mmol) in DMF (60 mL), which was stirred and cooled with ice, was added a solution of 2,6-pyridinedimethanol (5.00 g, 35.9 mmol) in DMF (30 mL), and stirred for 1 hour at a room temperature under Ar atmosphere. To the mixture was added a solution of tert-butyldimethylchlorosilane (6.54 g, 43.3 mmol) in DMF (40 mL), and stirred for additional 12 hours. TLC was used to confirm there was no starting material in the reaction mixture. Then, the mixture was subjected to extraction with EtOAc and 10% NaHCO3 aq. The organic layer was washed with sat. NaClaq., dried over anhydrous Na2SO4, and evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (Hex:EtOAc=5:1) to give 2-[(tert-butyldimethylsilyloxy)methyl]-6-hydroxymethylpyridine (1) (4.46 g, 49%) as a colorless oil.

Workup

  1. temperaturecooled with ice
  2. stirringstirred for additional 12 hours
  3. extractionThen, the mixture was subjected to extraction with EtOAc and 10% NaHCO3 aq. The organic layer
  4. washwas washed with sat. NaClaq
  5. dry with material, dried over anhydrous Na2SO4
  6. customevaporated under reduced pressure
  7. customto remove the solvent
  8. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=5:1)

Sources & evidence

ORD record
ord-c99b7afb08124b0783ebeb90ce15fc97
Source dataset
uspto-grants-2014_01
Patent number
US08633304B2

Linked notes

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