Hydrochloric Acid → 5-(2-Benzyloxyethoxy)pyrazine-2-carboxylic acid

HRID 2192911Notes

Reaction equation

HRID 2192911 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:15]1[N:16]=[CH:17][C:18]([C:21]([O:23]C)=[O:22])=[N:19][CH:20]=1.Cl.[OH-].[Na+]>CN(C=O)C.CO.O>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:15]1[N:16]=[CH:17][C:18]([C:21]([OH:23])=[O:22])=[N:19][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 121412-(Benzyloxy) ethanolHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 406081Methyl 5-chloropyrazine-2-carboxylate

Product 1

HCID 595710675-(2-Benzyloxyethoxy)pyrazine-2-carboxylic acidYield 34.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(benzyloxy)ethanol (1.94 g) in DMF (60 mL) was added 60% sodium hydride (510 mg) under ice-cooling, followed by stirring at room temperature for 30 minutes, and methyl 5-chloropyrazine-2-carboxylate (2 g) was added thereto in one portion in an ice bath, followed by stirring at room temperature for 15 minutes. To the reaction mixture was added 1 M hydrochloric acid in an ice bath, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1) to obtain a colorless oily substance. To a solution of the obtained colorless oily substance in methanol (50 mL) was added 1 M aqueous sodium hydroxide solution (15 mL) at room temperature, followed by stirring at room temperature for 2 hours. 1 M Hydrochloric acid was added to reaction mixture to adjust the pH to 2 under ice-cooling, followed by addition of water (about 200 mL). The resulting precipitate was collected by filtration while washing with a solvent (water:methanol=5:1), to obtain 5-[2-(benzyloxy)ethoxy]pyrazine-2-carboxylic acid (1.089 g) as a white solid.

Workup

  1. temperaturecooling
  2. customin one portion in an ice bath, followed
  3. stirringby stirring at room temperature for 15 minutes
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1)
  9. customto obtain a colorless oily substance
  10. stirringby stirring at room temperature for 2 hours
  11. temperaturecooling
  12. filtrationThe resulting precipitate was collected by filtration
  13. washwhile washing with a solvent (water:methanol=5:1)

Sources & evidence

ORD record
ord-023c78f134d549579f4b71dfaad326c0
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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