Dimethylformamide → 5-(tert-Butyldimethylsilyloxymethyl)-2-(hydroxymethyl)pyridine

HRID 1674148Notes

Reaction equation

HRID 1674148 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[O:17]1CCC[CH2:18]1.C([Li])CCC.CN(C)C=O>C(OCC)C>[Si:10]([O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH2:18][OH:17])=[N:3][CH:4]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 6425754Pyridine, 2-bromo-5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-HCID 178418339Butyllithium

Product 1

HCID 224732225-(tert-Butyldimethylsilyloxymethyl)-2-(hydroxymethyl)pyridineYield 64%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a mixture of 2-bromo-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (11 g) and tetrahydrofuran (450 mL) was added n-butyllithium (1.6 M hexane solution, 25.3 mL) at −78° C., and the reaction mixture was stirred for 1 hr. Then, N,N-dimethylformamide (3.17 mL) was added at −78° C., and the temperature of the mixture was raised to room temperature and stirred for 16 hr. The reaction mixture was diluted with diethyl ether, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in methanol (200 mL), sodium borohydride (1.95 g) was added at 0° C., and the reaction mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure, and the obtained residue was extracted with saturated aqueous ammonium chloride solution and ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (7.53 g, 64%).

Workup

  1. stirringstirred for 16 hr
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe obtained residue was dissolved in methanol (200 mL)
  6. additionsodium borohydride (1.95 g) was added at 0° C.
  7. stirringthe reaction mixture was stirred at room temperature for 2 hr
  8. customThe solvent was evaporated under reduced pressure
  9. extractionthe obtained residue was extracted with saturated aqueous ammonium chloride solution and ethyl acetate
  10. washThe ethyl acetate layer was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a17b3e3192cf4707ab5f522433295f82
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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