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

HRID 1760341Notes

Reaction equation

HRID 1760341 reaction equation
[CH:1]1([C:4](=O)[CH2:5][C:6]#[N:7])[CH2:3][CH2:2]1.CS(O)(=O)=O.[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.C1(C)C=CC=CC=1.[OH-].[Na+]>O>[CH:1]1([C:4]2[C:5]([C:6]#[N:7])=[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)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 98127633-Cyclopropyl-3-oxopropanenitrileHCID 53446970(2-Aminophenyl)(4-fluorophenyl)methanone methanesulfonate

Product 1

HCID 99657382-Cyclopropyl-4-(4'-fluorophenyl)quinoline-3-carbonitrileYield 99.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Into a glass flask having an internal volume of 300 mL, equipped with a stirring apparatus, a thermometer, a reflux condenser and a Dean-Stark apparatus, 11.6 g (106.6 mmol) of 3-cyclopropyl-3-oxopropanenitrile, 31.0 g (96.9 mmol) of 2-amino-4′-fluorobenzophenone methanesulfonate having a purity of 97.3% and 121 mL of toluene were put in an atmosphere of nitrogen, and reaction was carried out under 0.04 MPa at 80° C. for 2 hours while distilling off the formed water. After completion of the reaction, the reaction liquid was cooled to room temperature, 60 mL of water and 13.3 mL (106.4 mmol) of a 8 mol/L sodium hydroxide aqueous solution were added thereto to make the reaction liquid basic, followed by liquid separation, and the obtained organic layer was analyzed by high performance liquid chromatography (absolute quantitative analysis), whereupon 27.9 g (yield: 99%) of 2-cyclopropyl-4-(4′-fluorophenyl)quinoline-3-carbonitrile was formed.

Workup

  1. customInto a glass flask having
  2. customan internal volume of 300 mL, equipped with a stirring apparatus
  3. distillationwhile distilling off the formed water
  4. customAfter completion of the reaction
  5. customthe reaction liquid
  6. customthe reaction liquid basic
  7. customfollowed by liquid separation

Sources & evidence

ORD record
ord-89bac5472ee04f54b86bbb627260d13c
Source dataset
uspto-grants-2005_01
Patent number
US06841681B2

Reaction notes

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