3-Hydroxypyridine → Tert-butyl 2-(3-pyridyloxy)acetate

HRID 1698347Notes

Reaction equation

HRID 1698347 reaction equation
Br[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[OH:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[C:6]([O:5][C:3](=[O:4])[CH2:2][O:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 79713-HydroxypyridineHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetate

Product 1

HCID 22668053Tert-butyl 2-(3-pyridyloxy)acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of t-butyl bromoacetate (2 g, 10 mmol), 3-hydroxypyridine (1.5 g, 15 mmol), and K2CO3 (2.9 g, 21 mmol) in THF (20 mL) is stirred at 60° C. After 0.5 h, the reaction mixture is cooled down at room temperature and diluted with H2O, then extracted with EtOAc. The organic phase is washed with H2O, and brine, then dried over Na2SO4. The solution is filtered and the solvent is evaporated in vacuo. The residue is purified by silica gel column chromatography to give the title compound MS: 210 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 1.85 min.

Workup

  1. temperaturethe reaction mixture is cooled down at room temperature
  2. extractionextracted with EtOAc
  3. washThe organic phase is washed with H2O, and brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution is filtered
  6. customthe solvent is evaporated in vacuo
  7. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-80158afda2ff4b538477de4458713c4b
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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