Methanol → HCID 12802762, compound

HRID 1833379Notes

Reaction equation

HRID 1833379 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([CH3:17])=[CH:7][C:6]1=[O:18].[H-].[Na+].[C:25](=O)([O:29]CC)[O:26]CC.[CH3:33]O>>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([CH:17]([CH3:33])[C:25]([OH:29])=[O:26])=[CH:7][C:6]1=[O:18]

Participants

5

Reactant 4

HCID 887MethanolHCID 7766Diethyl CarbonateHCID 24758Sodium hydrideHCID 203756241-[(2-Chlorophenyl)methyl]-6-methoxy-4-methylquinolin-2(1H)-one

Product 1

HCID 12802762HCID 12802762, compoundYield 48%

Procedure

A mixture of 1-o-chlorobenzyl-4-methyl-6-methoxy-2-oxo-1,2-dihydroquinoline (2.5g.), oil-free sodium hydride (obtained from 2.5g. of a 50% w/w suspension as described in Example 1) and diethyl carbonate (50 ml.) was heated over 1 hour to reflux and the reflux maintained for 3 hours. The mixture was cooled and treated with methanol (2ml.) to destroy excess sodium hydride. Ether (200ml.) was added and the yellow precipitate was filtered off, washed with ether (50ml.), and dried, and was then suspended in dimethylformamide (100 ml.) containing methyl iodide (4 ml.). After 24 hours standing at room temperature, the mixture was diluted with water (200 ml.) and the aqueous mixture extracted with ether (3 × 100ml.). The combined ethereal extracts were washed with water (2 × 100ml.), and dried with magnesium sulphate, and the ether was evaporated. The residue, which comprised diethyl α-(1-o-chlorobenzyl-6-methoxy-2-oxo-1,2-dihydroquinol-4-yl)-α-methylmalonate, was dissolved in a solution of potassium hydroxide (3.6 g.) in water (4ml.) and ethanol (100ml.). The mixture was refluxed for 1 hour, cooled, and diluted with N-hydrochloric acid (100ml.). The resulting mixture was filtered, and the solid residue washed with water and crystallised from methanol (100ml.) to give α-(1-o-chlorobenzyl-6-methoxy-2-oxo-1,2-dihydroquinol-4-yl)propionic acid, m.p. 187°-188° C. in 48% yield.

Workup

  1. customobtained from 2.5g
  2. temperaturewas heated over 1 hour
  3. temperatureto reflux
  4. temperaturethe reflux maintained for 3 hours
  5. temperatureThe mixture was cooled
  6. customto destroy excess sodium hydride
  7. additionEther (200ml.) was added
  8. filtrationthe yellow precipitate was filtered off
  9. washwashed with ether (50ml.)
  10. customdried
  11. additioncontaining methyl iodide (4 ml.)
  12. additionthe mixture was diluted with water (200 ml.)
  13. extractionthe aqueous mixture extracted with ether (3 × 100ml.)
  14. washThe combined ethereal extracts were washed with water (2 × 100ml.)
  15. dry with materialdried with magnesium sulphate
  16. customthe ether was evaporated
  17. dissolutionwas dissolved in a solution of potassium hydroxide (3.6 g.) in water (4ml.) and ethanol (100ml.)
  18. temperatureThe mixture was refluxed for 1 hour
  19. temperaturecooled
  20. additiondiluted with N-hydrochloric acid (100ml.)
  21. filtrationThe resulting mixture was filtered
  22. washthe solid residue washed with water
  23. customcrystallised from methanol (100ml.)

Sources & evidence

ORD record
ord-387e7c6f1f77424999e28bfbd2806fdd
Source dataset
uspto-grants-1978_01
Patent number
US04066651

Reaction notes

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