Diethyl (ethoxymethylene)malonate → Ethyl 2-benzyl-8-hydroxy-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazine-7-carboxylate

HRID 747842Notes

Reaction equation

HRID 747842 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:17][CH:18]=[C:19]([C:25](OCC)=O)[C:20]([O:22][CH2:23][CH3:24])=[O:21])C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH:25]=[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:18]([OH:17])=[C:10]2[C:9]1=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6871Diethyl (ethoxymethylene)malonateHCID 8028TetrahydrofuranHCID 15143031-Benzylpiperazin-2-oneHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 3011066Ethyl 2-benzyl-8-hydroxy-1-oxo-3,4-dihydropyrrolo[1,2-a]pyrazine-7-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-benzylpiperazin-2-one (0.29 g, 1.54 mmol) and diethyl ethoxymethylenemalonate (0.35 g, 1.63 mmol) in toluene was heated in a sealed tube at 80° C. for 4 hours. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous DMF (10 mL), cooled to 0° C. under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 2.0 mL, 2.0 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was partitioned between ethyl acetate and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether, and the solid precipitated was filtered to provide the title compound.

Workup

  1. concentrationThe resultant mixture was concentrated under vacuum
  2. dissolutionThe residue was dissolved in anhydrous DMF (10 mL)
  3. temperaturecooled to 0° C. under an atmosphere of nitrogen
  4. concentrationconcentrated under vacuum
  5. customThe residue was partitioned between ethyl acetate and dilute aqueous HCl
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThe residue was triturated with diethyl ether
  12. customthe solid precipitated
  13. filtrationwas filtered

Sources & evidence

ORD record
ord-9d06fdaff6b5497284b2ecdf306e8cb8
Source dataset
uspto-grants-2008_07
Patent number
US07399763B2

Reaction notes

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