Ethyl Acetate → 3-[3-(2-Fluorophenoxymethyl)pyrrolidino]methyl-1H-pyrazin-2-one oxalate

HRID 890090Notes

Reaction equation

HRID 890090 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[O:4][CH2:5][CH:6]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[C:13]([O:18]C)=[N:14][CH:15]=[CH:16][N:17]=2)[CH2:7]1.[C:24](=[O:27])([OH:26])[O-].[Na+].[C:29]([O:32]CC)(=[O:31])C>C(O)C.Cl.C(OCC)(=O)C>[C:29]([OH:32])(=[O:31])[C:24]([OH:26])=[O:27].[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[O:4][CH2:5][CH:6]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[C:13](=[O:18])[NH:14][CH:15]=[CH:16][N:17]=2)[CH2:7]1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 222479393-[3-(2-Fluorophenoxymethyl)pyrrolidino]methyl-2-methoxypyrazine

Product 1

HCID 222485423-[3-(2-Fluorophenoxymethyl)pyrrolidino]methyl-1H-pyrazin-2-one oxalateYield 56%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 21866389Hydrogen chloride-ethyl acetateSolvent

Conditions

Temperature
60 °C

Procedure

After dissolving 245 mg of 3-[3-(2-fluorophenoxymethyl)pyrrolidino]methyl-2-methoxypyrazine in 5 ml of ethanol, 15 ml of 4N hydrogen chloride/ethyl acetate was added, and the mixture was heated to reflux for 8 hours and then stirred overnight at 60° C. Aqueous sodium bicarbonate solution was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: ethyl acetate/methanol). This was dissolved in a small amount of ethanol, and then 47 mg of oxalic acid anhydrous and ethyl acetate were added and the precipitate was filtered out to obtain the title compound (171 mg, 56% yield).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 8 hours
  4. washThe organic layer was washed with water and saturated brine in that order
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by NH silica gel column chromatography (solvent: ethyl acetate/methanol)
  8. dissolutionThis was dissolved in a small amount of ethanol
  9. addition47 mg of oxalic acid anhydrous and ethyl acetate were added
  10. filtrationthe precipitate was filtered out

Sources & evidence

ORD record
ord-96db85a7d9074514867b989e7018794a
Source dataset
uspto-grants-2006_02
Patent number
US06995144B2

Reaction notes

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