Hydrazine → 4-(Aminomethyl)-3-fluorobenzonitrile

HRID 1247271Notes

Reaction equation

HRID 1247271 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[F:11].[K].C1(=O)[NH:17]C(=O)C2=CC=CC=C12.NN>CN(C=O)C.C(O)C.O>[NH2:17][CH2:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][C:4]=1[F:11]

Participants

7

Reactant 3

HCID 9321HydrazineHCID 27831494-(Bromomethyl)-3-fluorobenzonitrileHCID 24194345Phthalimide potassium salt

Product 1

HCID 219054434-(Aminomethyl)-3-fluorobenzonitrileYield 4.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

4-(Bromomethyl)-3-fluorobenzonitrile (CAS 105942-09-4, 21 g) was dissolved in DMF (90 ml). Phthalimide potassium salt (19.64 g) was added and the mixture was stirred for 9 h at 130° C. After cooling to rt, the mixture was poured on ice. The solid was filtered off. Ethyl acetate and water were added and extracted with ethyl acetate. The organic phase was washed with water, dried, filtered and evaporated to give a light brown solid (14.1 g, 42% pure as judged by NMR). This solid was suspended in ethanol (50 ml). A solution of hydrazine in water (24%, 15 ml) was added and the mixture was refluxed for a total of 14 h. The mixture was filtered and the solvent was evaporated. The product was purified by chromatography (silica gel, CH2Cl2=>CH2Cl2/MeOH 4:1) to give 4-aminomethyl-3-fluoro-benzonitrile (0.63 g) as a brown oil.

Workup

  1. temperatureAfter cooling to rt
  2. additionthe mixture was poured on ice
  3. filtrationThe solid was filtered off
  4. additionEthyl acetate and water were added
  5. extractionextracted with ethyl acetate
  6. washThe organic phase was washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customto give a light brown solid (14.1 g, 42% pure as judged by NMR)
  11. temperaturethe mixture was refluxed for a total of 14 h
  12. filtrationThe mixture was filtered
  13. customthe solvent was evaporated
  14. customThe product was purified by chromatography (silica gel, CH2Cl2=>CH2Cl2/MeOH 4:1)

Sources & evidence

ORD record
ord-fd8d1b82a15d46f8bc3aa99fad952053
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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