3-Hydroxypyridine → 1,1-Dimethylethyl 2-(3-pyridinyloxy)propanoate

HRID 2112356Notes

Reaction equation

HRID 2112356 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1.Br[CH:11]([CH3:19])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C(=O)(O)[O-].[Na+]>CN(C=O)C>[N:6]1[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH:11]([CH3:19])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:5]=1

Participants

6

Reactant 4

HCID 79713-HydroxypyridineHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 545327tert-Butyl 2-bromopropanoate

Product 1

HCID 226680791,1-Dimethylethyl 2-(3-pyridinyloxy)propanoateYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of 1.20 g of sodium hydride (60% oil dispersion; 30.0 mmol) in 10 mL of dry DMF at room temperature were added dropwise 2.85 g of 3-hydroxypyridine (30 mmol) in 10 mL of dry DMF, maintaining the temperature below 40° C., and the mixture was stirred at room temperature for 90 min. Under ice-cooling, 6.28 g of tert-butyl 2-bromopropionate (30 mmol) in 10 mL of dry DMF were slowly added dropwise, maintaining the inner temperature within 5 to 10° C., and then the mixture was warmed to room temperature with stirring for 4 hours. After neutralizing with saturated sodium bicarbonate aq., the mixture was extracted with ethyl acetate. The organic layer was washed with water and then saturated brine, dried and evaporated. The residue was purified by column chromatography on silica gel (eluent: n-hexane:ethyl acetate=2:1) to give 4.15 g of tert-butyl 2-(pyridin-3-yl)oxypropionate (Yield: 62%) as a brown oil.

Workup

  1. temperaturemaintaining the temperature below 40° C.
  2. temperatureUnder ice-cooling
  3. temperaturemaintaining the inner temperature within 5 to 10° C.
  4. temperaturethe mixture was warmed to room temperature
  5. stirringwith stirring for 4 hours
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with water
  8. dry with materialsaturated brine, dried
  9. customevaporated
  10. customThe residue was purified by column chromatography on silica gel (eluent: n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-b0f1e67de5b84c25b40d0caca8478628
Source dataset
uspto-grants-2009_04
Patent number
USRE040703E1

Reaction notes

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