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

HRID 24282

Reaction equation

HRID 24282 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([CH:18]3[CH2:20][CH2:19]3)[C:9]=2[C:21](OC)=[O:22])=[CH:4][CH:3]=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].N1CCOCC1.S(=O)(=O)(O)O>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([CH:18]3[CH2:19][CH2:20]3)[C:9]=2[CH:21]=[O:22])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8083MorpholineHCID 9901664Methyl 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carboxylateHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydride

Product 1

HCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehydeYield 76.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-5 °C

Procedure

Methyl 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carboxylate (32.1 g, 100 mmol) and toluene (300 ml) were placed in a different 1000 ml three-necked flask, and the system was replaced by nitrogen and cooled to −5° C. To this solution was added dropwise the entire amount of a toluene solution prepared earlier by mixing sodium bis(2-methoxyethoxy)aluminum hydride and morpholine, while maintaining the inner temperature to not higher than 0° C., and after completion of the addition, the mixture was heated to room temperature and stirred for 3 hr. This reaction mixture was added dropwise to a 15% aqueous sulfuric acid solution (200 ml) while maintaining the inner temperature to not higher than 10° C. The organic layer was separated from the mixture and the aqueous layer was extracted with toluene (30 ml). The extract was combined with the organic layer obtained earlier. The mixture was washed with water (100 ml), dried over anhydrous sodium sulfate and concentrated. The obtained residue was recrystallized from diisopropyl ether to give 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde (22.4 g, yield 76%).

Workup

  1. customprepared earlier
  2. temperaturewhile maintaining the inner temperature to not higher than 0° C.
  3. additionafter completion of the addition
  4. temperaturethe mixture was heated to room temperature
  5. temperaturewhile maintaining the inner temperature to not higher than 10° C
  6. customThe organic layer was separated from the mixture
  7. extractionthe aqueous layer was extracted with toluene (30 ml)
  8. customobtained earlier
  9. washThe mixture was washed with water (100 ml)
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated
  12. customThe obtained residue was recrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-38f4f2db40754086badfc3196e414a65
Source dataset
uspto-grants-2005_02
Patent number
US06855824B2

Linked notes

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