Reaction #52560

Reaction equation

sulfuric acid

sodium bis(2-methoxyethoxy)aluminum hydride

morpholine

Methyl 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carboxylate

→

4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde

Yield 76.9%

Solvents

toluene

toluene

Conditions

Workup

1. 1
   Otherprepared earlier
2. 2
   Temperaturewhile maintaining the inner temperature to not higher than 0° C.
3. 3
   workup.ADDITIONafter completion of the addition
4. 4
   Temperaturethe mixture was heated to room temperature
5. 5
   Temperaturewhile maintaining the inner temperature to not higher than 10° C
6. 6
   OtherThe organic layer was separated from the mixture
7. 7
   Extractionthe aqueous layer was extracted with toluene (30 ml)
8. 8
   Otherobtained earlier
9. 9
   WashThe mixture was washed with water (100 ml)
10. 10
    Dryingdried over anhydrous sodium sulfate
11. 11
    Concentrationconcentrated
12. 12
    OtherThe obtained residue was recrystallized from diisopropyl ether

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%).

Source