Potassium Iodide → 5-[(2-Cyclopropyl-2-oxoethyl)amino]-2-fluoro-4-methylbenzonitrile

HRID 522472Notes

Reaction equation

HRID 522472 reaction equation
[NH2:1][C:2]1[C:3]([CH3:11])=[CH:4][C:5]([F:10])=[C:6]([CH:9]=1)[C:7]#[N:8].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:21][C:22]([CH:24]1[CH2:26][CH2:25]1)=[O:23]>CN(C)C=O>[CH:24]1([C:22](=[O:23])[CH2:21][NH:1][C:2]2[C:3]([CH3:11])=[CH:4][C:5]([F:10])=[C:6]([CH:9]=2)[C:7]#[N:8])[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 109208412-Bromo-1-cyclopropylethan-1-oneHCID 866774495-Amino-2-fluoro-4-methylbenzonitrile

Product 1

HCID 866912475-[(2-Cyclopropyl-2-oxoethyl)amino]-2-fluoro-4-methylbenzonitrileYield 76.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

5-Amino-2-fluoro-4-methylbenzonitrile (12 g, 80 mmol) was dissolved in anhydrous N,N-dimethylformamide (160 mL) under nitrogen, and potassium carbonate (13.27 g, 96 mmol) and potassium iodide (14.61 g, 88 mmol) were added as solids with stirring. The reaction was stirred for 5 minutes at room temperature and then bromomethyl cyclopropylketone (20.24 mL, 180 mmol) was added. The reaction mixture was heated to 60° C. for 3 hours, and then the solvents removed under reduced pressure. The residue was dissolved in EA (400 mL) and washed with 400 mL of water. The organic layer was dried over magnesium sulfate, and solvent was removed under reduced pressure. The residue was re-dissolved in a minimum amount of EA, and hexanes were added to bring the solution to 3:1 hexanes:EA by volume. The product precipitated out of solution and was collected by filtration to provide 5-(2-cyclopropyl-2-oxoethylamino)-2-fluoro-4-methylbenzonitrile (14.19 g, 61.2 mmol). LC/MS (m/z: 233, M+1)

Workup

  1. stirringThe reaction was stirred for 5 minutes at room temperature
  2. customthe solvents removed under reduced pressure
  3. dissolutionThe residue was dissolved in EA (400 mL)
  4. washwashed with 400 mL of water
  5. dry with materialThe organic layer was dried over magnesium sulfate, and solvent
  6. customwas removed under reduced pressure
  7. dissolutionThe residue was re-dissolved in a minimum amount of EA, and hexanes
  8. additionwere added
  9. customThe product precipitated out of solution
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-ac9115632cb448ada27275d2c1c9aee0
Source dataset
uspto-grants-2016_05
Patent number
US09333197B2

Reaction notes

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