Acetic Acid → ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

HRID 1061436Notes

Reaction equation

HRID 1061436 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH:8]([CH:11]2[CH2:13][CH2:12]2)[CH:9]=O)[C:3]=1[CH3:14].N1CCC[CH2:17][CH2:16]1.C(O)(=O)C.C([C:27](CC)([C:31]([O-:33])=O)[C:28]([O-:30])=[O:29])C>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:4]([C:3]=1[CH3:14])=[C:8]([CH:11]1[CH2:13][CH2:12]1)[CH:9]=[C:27]([C:28]([O:30][CH2:16][CH3:17])=[O:29])[C:31]2=[O:33]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 69515632,2-DiethylpropanedioateHCID 186293552-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-acetaldehyde

Product 1

HCID 12071709ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

1.31 g of 2-(4-chloro-3-methyl-2-pyridyl)-2-cyclopropylethanal (XII) was dissolved in 45 ml of anhydrous ethanol, and 1.48 ml of piperidine, 1.48 ml of acetic acid and 4.75 ml of diethylmalonate were added thereto and the resulting mixture was heated at 100° C. for 5 hours. The solvent was distilled off under reduced pressure, and thereafter, the resulting mixture was diluted with ether and the resulting organic layer was washed with water and saturated salt water, and thereafter, dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. 30 ml of Dowtherm A was added to the resulting residue, which was heated at 240° C. for 30 minutes. The reaction solution was purified directly by silica gel column chromatography (eluent; hexane hexane:ethyl acetate=1:1) to obtain 1.45 g of ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (XIII).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. additionthe resulting mixture was diluted with ether
  3. washthe resulting organic layer was washed with water and saturated salt water
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. addition30 ml of Dowtherm A was added to the resulting residue, which
  7. temperaturewas heated at 240° C. for 30 minutes
  8. customThe reaction solution was purified directly by silica gel column chromatography (eluent; hexane hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-5aced1a80fb14411ac27540ab65a9362
Source dataset
uspto-grants-2003_02
Patent number
US06525066B2

Reaction notes

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