Hydrochloric Acid → 1-cyclopropyl-9-methyl-8-(1-methylisoindoline-5-yl)-4-oxo-4H-quinolizine-3-carboxylic acid

HRID 1061438Notes

Reaction equation

HRID 1061438 reaction equation
C(O)C.Cl.[CH:5]1([C:8]2[CH:9]=[C:10]([C:30]([O:32]CC)=[O:31])[C:11](=[O:29])[N:12]3[C:17]=2[C:16]([CH3:18])=[C:15]([C:19]2[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=2)[CH:24]([CH3:28])[NH:23][CH2:22]4)[CH:14]=[CH:13]3)[CH2:7][CH2:6]1>C1COCC1>[CH:5]1([C:8]2[CH:9]=[C:10]([C:30]([OH:32])=[O:31])[C:11](=[O:29])[N:12]3[C:17]=2[C:16]([CH3:18])=[C:15]([C:19]2[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=2)[CH:24]([CH3:28])[NH:23][CH2:22]4)[CH:14]=[CH:13]3)[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 18629334ethyl 1-cyclopropyl-9-methyl-8-(1-methylisoindoline-5-yl)-4-oxo-4H-quinolizine-3-carboxylate

Product 1

HCID 186293251-cyclopropyl-9-methyl-8-(1-methylisoindoline-5-yl)-4-oxo-4H-quinolizine-3-carboxylic acidYield 47.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

7.6 ml ethanol, 2.5 ml of THF and 1.3 ml of 1N hydrochloric acid were added to 312.5 mg of ethyl 1-cyclopropyl-9-methyl-8-(1-methylisoindoline-5-yl)-4-oxo-4H-quinolizine-3-carboxylate (XIV) and the resulting mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure and water was added to the resulting residue and the resulting residue was washed with ethyl acetate, and thereafter, the resulting water layer was concentrated under reduced pressure. 10 ml of water, 5 ml of ethanol and 3 ml of 1N sodium hydroxide were added to the residue, which was stirred at 50° C. for 3 hours. The reaction solution was concentrated under reduced pressure, and thereafter, dissolved in 4 ml of water and neutralized with 1N hydrochloric acid. The precipitated crystal was separated by filtering to obtain 139.1 mg of 1-cyclopropyl-9-methyl-8-(1-methylisoindoline-5-yl)-4-oxo-4H-quinolizine-3-carboxylic acid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure and water
  2. additionwas added to the resulting residue
  3. washthe resulting residue was washed with ethyl acetate
  4. concentrationthe resulting water layer was concentrated under reduced pressure
  5. addition10 ml of water, 5 ml of ethanol and 3 ml of 1N sodium hydroxide were added to the residue, which
  6. stirringwas stirred at 50° C. for 3 hours
  7. concentrationThe reaction solution was concentrated under reduced pressure
  8. dissolutiondissolved in 4 ml of water and neutralized with 1N hydrochloric acid
  9. customThe precipitated crystal was separated
  10. filtrationby filtering

Sources & evidence

ORD record
ord-ea370e1b91e648cc93528d451eaa5a72
Source dataset
uspto-grants-2003_02
Patent number
US06525066B2

Reaction notes

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