Water → 6-[2-[4-[2-(2-Fluorophenyl)acetyl]piperidino]ethyl]-1H-pyrazin-2-one

HRID 890102Notes

Reaction equation

HRID 890102 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:11].C(=O)([O-])[O-].[K+].[K+].C([O:28][C:29]1[CH:34]=[N:33][CH:32]=[C:31]([CH:35]=[CH2:36])[N:30]=1)(C)(C)C.O>CN(C)C=O.C(OCC)(=O)C>[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([CH:12]1[CH2:13][CH2:14][N:15]([CH2:36][CH2:35][C:31]2[NH:30][C:29](=[O:28])[CH:34]=[N:33][CH:32]=2)[CH2:16][CH2:17]1)=[O:11]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 222481242-(2-Fluorophenyl)-1-(piperidin-4-yl)ethanone hydrochlorideHCID 222482762-Tert-butoxy-6-vinylpyrazine

Product 1

HCID 222484606-[2-[4-[2-(2-Fluorophenyl)acetyl]piperidino]ethyl]-1H-pyrazin-2-oneYield 2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 1.00 g of 2-(2-fluorophenyl)-1-(piperidin-4-yl)ethanone hydrochloride in 8 ml of N,N-dimethylformamide, 643 mg of potassium carbonate and 899 mg of 2-tert-butoxy-6-vinylpyrazine were added while stirring, and the stirring was continued for 64 hours at 100° C. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine 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: n-hexane/ethyl acetate). Three milliters of 4N hydrogen chloride/ethyl acetate was added to the obtained product and the mixture was stirred for 2.5 hours at room temperature. A 1N sodium hydroxide solution was added to the reaction solution and extraction was performed with dichloromethane. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: chloroform/methanol/ammonia water) to obtain the title compound (27 mg, 2 yield).

Workup

  1. additionwere added
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)
  6. additionThree milliters of 4N hydrogen chloride/ethyl acetate was added to the obtained product
  7. stirringthe mixture was stirred for 2.5 hours at room temperature
  8. additionA 1N sodium hydroxide solution was added to the reaction solution and extraction
  9. washThe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationthe solvent was distilled off under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (solvent: chloroform/methanol/ammonia water)

Sources & evidence

ORD record
ord-e6e3e785f5f843eeb4850f4bfaf20a25
Source dataset
uspto-grants-2006_02
Patent number
US06995144B2

Reaction notes

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