3-Pyridinemethanol → 1,1-Dimethylethyl 2-(3-pyridinylmethoxy)acetate

HRID 912478Notes

Reaction equation

HRID 912478 reaction equation
[H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][OH:10])[CH:4]=1.Br[CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C(=O)(O)[O-].[Na+]>C1COCC1.O>[C:16]([O:15][C:13](=[O:14])[CH2:12][O:10][CH2:9][C:5]1[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 75103-PyridinemethanolHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 516892Sodium Bicarbonate

Product 1

HCID 247635281,1-Dimethylethyl 2-(3-pyridinylmethoxy)acetateYield 33.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of 4.4 g of sodium hydride (60% oil dispersion; 110 mmol) in 300 mL of THF were added dropwise 10.91 g of 3-pyridinemethanol (100 mmol) in 20 mL of THF at room temperature, and the mixture was stirred at room temperature for 2 hours. The resulting white suspension was ice-cooled, and 19.51 g of tert-butyl bromoacetate (100 mmol) in 20 mL of THF was added dropwise, maintaining the inner temperature within 10 to 12° C. The suspension was warmed to room temperature with stirring for 3 hours, and then left overnight. After adding water and saturated sodium bicarbonate aq., the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried and evaporated. The residue was purified by column chromatography on silica gel (gradient elution with n-hexane:ethyl-acetate=1:1 to ethyl acetate) to give 7.56 g of tert-butyl(pyridin-3-yl)methoxyacetate (33.8%) as a light brown oil.

Workup

  1. temperaturecooled
  2. temperaturemaintaining the inner temperature within 10 to 12° C
  3. temperatureThe suspension was warmed to room temperature
  4. stirringwith stirring for 3 hours
  5. waitleft overnight
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. customdried
  9. customevaporated
  10. customThe residue was purified by column chromatography on silica gel (gradient elution with n-hexane:ethyl-acetate=1:1 to ethyl acetate)

Sources & evidence

ORD record
ord-7464bdad2eb94530a97292dbb0bf6cff
Source dataset
uspto-grants-2011_09
Patent number
US08026239B2

Reaction notes

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