Reaction #52559

Reaction equation

sulfuric acid

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

Lithium aluminum hydride

morpholine

→

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

Yield 77.9%

Solvents

tetrahydrofuran

tetrahydrofuran

toluene

Conditions

Workup

1. 1
   workup.ADDITIONwas added as a solvent
2. 2
   workup.ADDITIONafter completion of the addition
3. 3
   TemperatureThis solution was cooled to 0° C.
4. 4
   Othera solution obtained
5. 5
   workup.ADDITIONwas added dropwise to this solution
6. 6
   Temperaturewhile maintaining the inner temperature to not higher than 0° C
7. 7
   workup.ADDITIONAfter the completion of the addition
8. 8
   workup.STIRRINGthe mixture was stirred for 2 more hours at 10 to 20° C
9. 9
   Temperaturewhile maintaining the inner temperature to not higher than 10° C.
10. 10
    OtherThe organic layer was separated from the mixture
11. 11
    Extractionthe aqueous layer was extracted with toluene (10 ml)
12. 12
    Otherobtained earlier
13. 13
    Washthe mixture was washed with water (30 ml)
14. 14
    Dryingdried over anhydrous sodium sulfate
15. 15
    Otherlow boiling point components, such as the solvent and the like, were removed under reduced pressure
16. 16
    OtherThe obtained residue was purified by column chromatography (eluent: hexane-ethyl acetate mixture)

Procedure

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.

Source