Hydrochloric Acid → HCID 20375610, compound

HRID 1390283Notes

Reaction equation

HRID 1390283 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[C:7](=[O:20])[CH:6]=[C:5]2[CH3:21].[H-].[Na+].[CH3:24]O.Cl.[C:27](=O)([O:31]CC)[O:28]CC>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[C:7](=[O:20])[CH:6]=[C:5]2[CH:21]([CH3:24])[C:27]([OH:31])=[O:28]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 7766Diethyl CarbonateHCID 24758Sodium hydrideHCID 203756136-Chloro-1-[(4-chlorophenyl)methyl]-4-methylquinolin-2(1H)-one

Product 1

HCID 20375610HCID 20375610, compoundYield 43%

Procedure

6-Chloro-1-(4-chlorobenzyl)-1,2-dihydro-4-methyl-2-oxoquinoline (7.9 g.) was added to a suspension of sodium hydride (6.0 g., 60% w/w dispersion in oil, washed as in Example 1) in diethyl carbonate (100 ml.). The mixture was then stirred and heated under reflux for 3 hours. A small quantity of methanol was added to the cooled suspension to destroy any remaining sodium hydride, and the mixture was then poured into ether (1 l.) to give a solid which was collected and washed well with ether. This solid (16 g.) was suspended in dimethylformamide (40 ml.), and methyl iodide (30.0 g.) was added. The mixture was stirred at room temperature for 1 hour and then heated under reflux on the steam-bath for 1 hour. The mixture was cooled and poured into water (200 ml.) to give an oil which was extracted into ethyl acetate, washed three times with water, and, after drying over magnesium sulphate, was recovered by evaporation under reduced pressure. The residual oil (4.8 g.), which comprised diethyl α-[6-chloro-1-(4-chlorobenzyl)-1,2-dihydro-2-oxoquinol-4-yl]-α-methylmalonate, was dissolved in a mixture of ethanol (50 ml.) and aqueous 40% w/v sodium hydroxide (4ml.), and heated under reflux for 2 hours. The resultant suspension was poured into water (200ml.) to give a solution which was adjusted to pH 3 by addition of concentrated hydrochloric acid. The precipitate was collected by filtration, washed with water, drained well, and recrystallised from aqueous ethanol to give α-[6-chloro-1-(4-chlorobenzyl)-1,2-dihydro-2-oxoquinol-4-yl]propionic acid, m.p. 192.5-193.5° C., (decomposition) in 43% yield.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 3 hours
  3. customto destroy any remaining sodium hydride
  4. additionthe mixture was then poured into ether (1 l.)
  5. customto give a solid which
  6. customwas collected
  7. washwashed well with ether
  8. additionmethyl iodide (30.0 g.) was added
  9. stirringThe mixture was stirred at room temperature for 1 hour
  10. temperatureheated
  11. temperatureunder reflux on the steam-bath for 1 hour
  12. temperatureThe mixture was cooled
  13. additionpoured into water (200 ml.)
  14. customto give an oil which
  15. extractionwas extracted into ethyl acetate
  16. washwashed three times with water
  17. dry with materialafter drying over magnesium sulphate
  18. customwas recovered by evaporation under reduced pressure
  19. dissolutionwas dissolved in a mixture of ethanol (50 ml.) and aqueous 40%
  20. temperatureheated
  21. temperatureunder reflux for 2 hours
  22. additionThe resultant suspension was poured into water (200ml.)
  23. customto give a solution which
  24. filtrationThe precipitate was collected by filtration
  25. washwashed with water
  26. customrecrystallised from aqueous ethanol

Sources & evidence

ORD record
ord-0d97f35390344680becf5022919c4d7b
Source dataset
uspto-grants-1979_02
Patent number
US04138490

Reaction notes

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