Sulfuric Acid → 2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehyde

HRID 24281

Reaktionsgleichung

Reaktionsgleichung von HRID 24281
[H-].[Al+3].[Li+].[H-].[H-].[H-].N1CCOCC1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH:30]3[CH2:32][CH2:31]3)[C:21]=2[C:33](OC)=[O:34])=[CH:16][CH:15]=1.S(=O)(=O)(O)O>O1CCCC1.C1(C)C=CC=CC=1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH:30]3[CH2:31][CH2:32]3)[C:21]=2[CH:33]=[O:34])=[CH:16][CH:15]=1

Komponenten

7

Edukt 4

HCID 1118Sulfuric AcidHCID 8083MorpholineHCID 9901664Methyl 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carboxylateHCID 21226445Aluminium lithium hydride

Produkt 1

HCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehydeAusbeute 77,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Lithium aluminum hydride (0.569 g, 15 mmol) was placed in a 50 ml volume three-necked flask equipped with a thermometer, a magnetic stirrer and a dropping funnel, and tetrahydrofuran (10 ml) was added as a solvent, followed by replacement of the system with nitrogen. To this solution was added dropwise morpholine (4.18 g, 48 mmol) gradually at room temperature, and after completion of the addition, the mixture was stirred at room temperature for 1 hr. This solution was cooled to 0° C. and a solution obtained by dissolving methyl 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carboxylate (3.21 g, 10 mmol) in tetrahydrofuran (9.63 g) was added dropwise to this solution while maintaining the inner temperature to not higher than 0° C. After the completion of the addition, the mixture was stirred for 2 more hours at 10 to 20° C. This reaction mixture was added dropwise to a 15% aqueous sulfuric acid solution (50 ml) while maintaining the inner temperature to not higher than 10° C., and then, toluene (50 ml) was added to the mixture. The organic layer was separated from the mixture and the aqueous layer was extracted with toluene (10 ml). The extract was combined with the organic layer obtained earlier and the mixture was washed with water (30 ml), dried over anhydrous sodium sulfate, then low boiling point components, such as the solvent and the like, were removed under reduced pressure. The obtained residue was purified by column chromatography (eluent: hexane-ethyl acetate mixture) to give 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde (2.27 g, yield 77%) as a pale-yellow solid having the following properties.

Aufarbeitung

  1. additionwas added as a solvent
  2. additionafter completion of the addition
  3. temperatureThis solution was cooled to 0° C.
  4. customa solution obtained
  5. additionwas added dropwise to this solution
  6. temperaturewhile maintaining the inner temperature to not higher than 0° C
  7. additionAfter the completion of the addition
  8. stirringthe mixture was stirred for 2 more hours at 10 to 20° C
  9. temperaturewhile maintaining the inner temperature to not higher than 10° C.
  10. customThe organic layer was separated from the mixture
  11. extractionthe aqueous layer was extracted with toluene (10 ml)
  12. customobtained earlier
  13. washthe mixture was washed with water (30 ml)
  14. dry with materialdried over anhydrous sodium sulfate
  15. customlow boiling point components, such as the solvent and the like, were removed under reduced pressure
  16. customThe obtained residue was purified by column chromatography (eluent: hexane-ethyl acetate mixture)

Quellen und Nachweise

ORD-Eintrag
ord-ca245234456d4ee78ebb12b4feaeb582
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06855824B2

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