Diethyl (ethoxymethylene)malonate → HCID 15632053, compound

HRID 407196Notes

Reaction equation

HRID 407196 reaction equation
C([N-]C(C)C)(C)C.[Li+].[N:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[C:10]=1[CH3:16].C([O:19][CH:20]=[C:21]([C:27](OCC)=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23])C.[Cl-].[NH4+]>C1COCC1>[CH3:15][C:11]1[C:10]2[N:9]([C:20](=[O:19])[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:27][CH:16]=2)[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 6871Diethyl (ethoxymethylene)malonateHCID 114202,3-LutidineHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 15632053HCID 15632053, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of lithium diisopropylamide (1.8 M in THF, 64.8 mL, 117 mmol) in 135 mL of THF at −78° C. was added a solution of 2,3-lutidine (10.0 g, 93.0 mol) in 62 mL of THF dropwise over 10 min. After an additional 40 min, a solution diethyl ethoxymethylenemalonate (21.7 mL, 107 mmol) in 30 mL of THF was added slowly over 15 min, and the reaction was slowly warmed to rt. After 2.5 h, the mixture was treated with saturated aqueous ammonium chloride and extracted 3× with dichlormethane. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude intermediate was dissolved in 100 mL of o-xylene and heated to reflux for 16 h. The reaction was concentrated in vacuo and the resultant residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide ethyl 9-methyl-4-oxo-4H-quinolizine-3-carboxylate that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 232.1 for [M+H]+.

Workup

  1. waitAfter 2.5 h
  2. extractionextracted 3× with dichlormethane
  3. dry with materialThe combined organic fractions were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude intermediate was dissolved in 100 mL of o-xylene
  7. temperatureheated
  8. temperatureto reflux for 16 h
  9. concentrationThe reaction was concentrated in vacuo
  10. customthe resultant residue was purified via silica gel chromatography
  11. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-7c85495f3c7148ddba6db942f7f2898d
Source dataset
uspto-grants-2014_06
Patent number
US08754220B2

Reaction notes

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