Sodium Hydroxide → 3-[4-[2-Fluoro-2-(2-fluorophenyl)ethyl]piperidino]methyl-1H-pyrazin-2-one

HRID 606230Notes

Reaction equation

HRID 606230 reaction equation
[F:1][CH:2]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])[CH2:3][CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C([O:21][C:22]1[C:23]([CH:28]=O)=[N:24][CH:25]=[CH:26][N:27]=1)(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[F:1][CH:2]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])[CH2:3][CH:4]1[CH2:5][CH2:6][N:7]([CH2:28][C:23]2[C:22](=[O:21])[NH:27][CH:26]=[CH:25][N:24]=2)[CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 222482803-(tert-Butoxy)pyrazine-2-carbaldehydeHCID 222485974-[2-Fluoro-2-(2-fluorophenyl)ethyl]piperidine

Product 1

HCID 222479623-[4-[2-Fluoro-2-(2-fluorophenyl)ethyl]piperidino]methyl-1H-pyrazin-2-oneYield 5.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 64 mg of 4-[2-fluoro-2-(2-fluorophenyl)ethyl]piperidine in 3 ml of tetrahydrofuran, 61 mg of 3-tert-butoxy-2-pyrazinecarboxaldehyde and 90 mg of sodium triacetoxyborohydride were added while stirring, and the stirring was continued overnight at room temperature. A 1N sodium hydroxide solution 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). Two milliliters of a 4N hydrogen chloride/ethyl acetate solution was added to the obtained product while stirring, and the stirring was continued 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. Diethyl ether/n-hexane was added to the residue and the insoluble portion was filtered out to obtain the title compound (5 mg, 5% 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. additionTwo milliliters of a 4N hydrogen chloride/ethyl acetate solution was added to the obtained product
  7. stirringwhile stirring
  8. waitthe stirring was continued for 2.5 hours at room temperature
  9. additionA 1N sodium hydroxide solution was added to the reaction solution and extraction
  10. washThe organic layer was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. distillationthe solvent was distilled off under reduced pressure
  13. additionDiethyl ether/n-hexane was added to the residue
  14. filtrationthe insoluble portion was filtered out

Sources & evidence

ORD record
ord-6474ad18de4648b0bce07a7dbdb3a76c
Source dataset
uspto-grants-2011_03
Patent number
US07915274B2

Reaction notes

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