Hydrochloric Acid → (2-Amino-5-chlorophenyl)(cyclopropyl)methanone

HRID 1877993Notes

Reaction equation

HRID 1877993 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:3]=1[C:4]#N.[CH:11]1([Mg]Br)[CH2:13][CH2:12]1.Cl.C(=O)([O-])[OH:18].[Na+]>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:3]=1[C:4]([CH:11]1[CH2:13][CH2:12]1)=[O:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 800192-Amino-5-chlorobenzonitrileHCID 516892Sodium BicarbonateHCID 178418630HCID 178418630, compound

Product 1

HCID 9837035(2-Amino-5-chlorophenyl)(cyclopropyl)methanoneYield 83%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-Amino-5-chlorobenzonitrile (500 mg, 3.28 mmol) was dissolved in THF (10 mL), and while stirring the reaction solution at 0° C., cyclopropyl magnesium bromide (0.5 M THF solution, 26.4 mL) was added dropwise thereto. The reaction solution was stirred overnight under heating at 80° C., followed by ice-cooling, and 2 N hydrochloric acid was added thereto under ice-cooling. After the reaction solution was stirred at room temperature for 2 hours, the solution was diluted with ethyl acetate and then neutralized with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated and washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1), whereby (2-amino-5-chlorophenyl)(cyclopropyl)methanone (453 mg, 83%) was obtained as a yellow solid.

Workup

  1. stirringThe reaction solution was stirred overnight
  2. temperatureunder heating at 80° C.
  3. temperaturecooling
  4. temperatureunder ice-cooling
  5. stirringAfter the reaction solution was stirred at room temperature for 2 hours
  6. customThe organic layer was separated
  7. washwashed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. customAfter the drying agent was removed by filtration
  10. customthe solvent was evaporated under reduced pressure
  11. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1)

Sources & evidence

ORD record
ord-f390f559ef4d4673a76069cb3a17b93e
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

Loading…