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

HRID 1061443
Notes
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Reaction equation

HRID 1061443 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]=1OC.N1CCC[CH2:18][CH2:17]1.[C:22](O)(=O)C.C([C:28](CC)([C:32]([O-:34])=O)[C:29]([O-:31])=[O:30])C>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:4]([C:3]=1[CH3:22])=[C:8]([CH:11]1[CH2:12][CH2:13]1)[CH:9]=[C:28]([C:29]([O:31][CH2:17][CH3:18])=[O:30])[C:32]2=[O:34]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 69515632,2-DiethylpropanedioateHCID 186293572-(4-Chloro-3-methoxy-2-pyridyl)-2-cyclopropylethanal

Product 1

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

Reagents, catalysts & solvents 1

HCID 702
Ethanol
Solvent

Conditions

Temperature
100 °C

Procedure

0.85 g of 2-(4-chloro-3-methoxy-2-pyridyl)-2-cyclopropylethanal (XII) was dissolved in 27 ml of anhydrous ethanol, and 0.89 ml of piperidine, 0.89 ml of acetic acid and 2.85 ml of diethylmalonate were added thereto and the resulting mixture was heated at 100° C. for 5.5 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. 20 ml of Dowtherm A was added to the resulting residue and the resulting mixture 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 0.67 g of ethyl 8-chloro-1-cyclopropyl-9-methoxy-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. addition20 ml of Dowtherm A was added to the resulting residue
  7. temperaturethe resulting mixture was 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-87278831ee984c2488cb51764c2426e9
Source dataset
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06525066B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes