Acetonitrile → (2Z)-3-Amino-3-[4-(trifluoromethyl)phenyl]prop-2-enenitrile

HRID 2389803Notes

Reaction equation

HRID 2389803 reaction equation
[CH:1]([NH:4]C(C)C)(C)[CH3:2].[Li+].CCC[CH2-].C(#N)C.[F:16][C:17]([F:27])([F:26])[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>C1COCC1.O>[NH2:23]/[C:22](/[C:21]1[CH:24]=[CH:25][C:18]([C:17]([F:26])([F:27])[F:16])=[CH:19][CH:20]=1)=[CH:2]\[C:1]#[N:4]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 61028n-Butyl lithiumHCID 67995Benzonitrile, 4-(trifluoromethyl)-

Product 1

HCID 5524790(2Z)-3-Amino-3-[4-(trifluoromethyl)phenyl]prop-2-enenitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

28.1 g (278 mmol) of diisopropylamine are introduced into 450 ml of THF at −70° C. in a three-neck flask with mechanical stirrer under argon. 148 ml of N-butyllithium solution (1.6 M in hexane, 237 mmol) are added dropwise at such a rate that the temperature does not rise above −60° C. The mixture is stirred for 10 min and then a solution of 12.9 ml (245 mmol) of acetonitrile in 100 ml of THF is slowly added dropwise, and the suspension is stirred for 30 min. Then a solution of 28 g (164 mmol) of 4-(trifluoromethyl)benzonitrile in 100 ml of THF is added dropwise, and the mixture is stirred at −70° C. for 20 min. It is allowed to reach RT slowly and is stirred at RT for a further 16 h. 150 ml of water are added, most of the THF is distilled off, and water and dichloromethane are added. The organic phase is washed with saturated aqueous sodium chloride solution. Removal of the solvent results in dark crystals which are purified by stirring with diisopropyl ether (40 ml once, 20 ml twice). The crystals are filtered off, washed with petroleum ether and dried. 27 g (78% of theory) of the product are obtained as a solid.

Workup

  1. customdoes not rise above −60° C
  2. stirringthe suspension is stirred for 30 min
  3. stirringthe mixture is stirred at −70° C. for 20 min
  4. customto reach RT
  5. stirringis stirred at RT for a further 16 h
  6. distillationis distilled off
  7. additionwater and dichloromethane are added
  8. washThe organic phase is washed with saturated aqueous sodium chloride solution
  9. customRemoval of the solvent
  10. customresults in dark crystals which
  11. customare purified
  12. stirringby stirring with diisopropyl ether (40 ml once
  13. filtrationThe crystals are filtered off
  14. washwashed with petroleum ether
  15. customdried
  16. custom27 g (78% of theory) of the product are obtained as a solid

Sources & evidence

ORD record
ord-3a4b4355a1de4d31acfd76c8e186a7b2
Source dataset
uspto-grants-2012_09
Patent number
US08273752B2

Reaction notes

Loading…