Methanesulfonic Acid → 2-Cyclopropyl-4-(4'-fluorophenyl)quinoline-3-carbonitrile

HRID 1760338Notes

Reaction equation

HRID 1760338 reaction equation
CS(O)(=O)=O.[CH:6]1([C:9](=O)[CH2:10][C:11]#[N:12])[CH2:8][CH2:7]1.[NH2:14][C:15]1[CH:29]=[CH:28][CH:27]=[CH:26][C:16]=1[C:17]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=O.[OH-].[Na+]>O.C1CCCCC1.C1(C)C=CC=CC=1>[CH:6]1([C:9]2[C:10]([C:11]#[N:12])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:16]3[C:15](=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:14]=2)[CH2:8][CH2:7]1

Participants

8

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 98127633-Cyclopropyl-3-oxopropanenitrileHCID 98372872-Amino-4'-fluorobenzophenone

Product 1

HCID 99657382-Cyclopropyl-4-(4'-fluorophenyl)quinoline-3-carbonitrileYield 95.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8078CyclohexaneSolvent

Procedure

Into a glass flask having an internal volume of 200 mL, equipped with a stirring apparatus, a thermometer, a reflux condenser and a Dean-Stark apparatus, 80 mL of toluene and 20 mL of cyclohexane were put in an atmosphere of nitrogen, and 2.94 g (30.6 mmol) of methanesulfonic acid, 3.50 g (32.1 mmol) of 3-cyclopropyl-3-oxopropanenitrile and 6.59 g (30.6 mmol) of 2-amino-4′-fluorobenzophenone were added thereto with stirring. Then, the temperature was raised, and reaction was carried out at a temperature of from 90 to 95° C. for 4 hours while distilling off the formed water. After completion of the reaction, the reaction liquid was cooled to room temperature, and 100 mL of water and 5.5 mL (44.0 mmol) of 8 mol/L sodium hydroxide aqueous solution were added to make the reaction liquid basic. The obtained reaction liquid was extracted with 200 mL of ethyl acetate twice, then the organic layer was separated, and 2 g of anhydrous magnesium sulfate, 2 g of silica gel and 2 g of activated carbon were added, followed by stirring at room temperature for 1 hour. After filtration, the filtrate was concentrated under reduced pressure to obtain 8.45 g of 2-cyclopropyl-4-(4′-fluorophenyl)quinoline-3-carbonitrile as a pale yellow solid with a purity of 99% (area percentage by high performance liquid chromatography) (yield: 95%).

Workup

  1. customInto a glass flask having
  2. customan internal volume of 200 mL, equipped with a stirring apparatus
  3. additionwere added
  4. temperatureThen, the temperature was raised
  5. customreaction
  6. distillationwhile distilling off the formed water
  7. customAfter completion of the reaction
  8. customthe reaction liquid
  9. customthe reaction liquid basic
  10. customThe obtained reaction liquid
  11. extractionwas extracted with 200 mL of ethyl acetate twice
  12. customthe organic layer was separated
  13. addition2 g of anhydrous magnesium sulfate, 2 g of silica gel and 2 g of activated carbon were added
  14. stirringby stirring at room temperature for 1 hour
  15. filtrationAfter filtration
  16. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-652b48b8ee274eb3aa8980c48da4dd08
Source dataset
uspto-grants-2005_01
Patent number
US06841681B2

Reaction notes

Loading…