Oxygen → 2-Amino-5-cyano-N,3-dimethylbenzamide

HRID 1511170Notes

Reaction equation

HRID 1511170 reaction equation
C1CCC=CCCC=1.O=O.[C-:11]#[N:12].[Na+].[NH2:14][C:15]1[C:24]([CH3:25])=[CH:23][C:22](Br)=[CH:21][C:16]=1[C:17]([NH:19][CH3:20])=[O:18]>Cl[Ni]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Zn]>[NH2:14][C:15]1[C:24]([CH3:25])=[CH:23][C:22]([C:11]#[N:12])=[CH:21][C:16]=1[C:17]([NH:19][CH3:20])=[O:18]

Participants

7

Reactant 4

HCID 977Oxygen2×HCID 8135cis,cis-1,5-CyclooctadieneHCID 8929Sodium CyanideHCID 442275752-amino-5-bromo-N,3-dimethylbenzamide

Product 1

HCID 251572822-Amino-5-cyano-N,3-dimethylbenzamide

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 178479585HCID 178479585, compoundCatalyst

Procedure

A reaction flask was charged with of [1,1′-bis(diphenylphosphino)ferrocene]-dichloronickel (68 mg, 0.099 mmol), zinc (130 mg, 1.99 mmol), 1,5-cyclooctadiene (28.3 mg, 0.262 mmol) and oxygen-free acetonitrile (4 mL) under a nitrogen atmosphere in a glovebox. After stirring for 2 h at room temperature, sodium cyanide (0.55 g, 11.22 mmol, ground prior to use), 2-amino-5-bromo-N,3-dimethylbenzamide (prepared by the method of Reference Example 1) (2.43 g, 9.99 mmol) and more oxygen-free acetonitrile (8 mL) were added to the reaction mixture. The flask was removed from the glovebox while maintaining a nitrogen atmosphere, and the reaction mixture was then heated at reflux (about 82° C.) while being vigorously stirred. After about 2 h and 25 minutes, HPLC analysis of the reaction mixture indicated about 96% conversion of the 2-amino-5-bromo-N,3-dimethylbenzamide with 2-amino-5-cyano-N,3-dimethylbenzamide being the major product. A portion of the reaction mixture (0.05 mL) was withdrawn and evaporated to dryness to give an analytical sample for 1H NMR analysis.

Workup

  1. additionwere added to the reaction mixture
  2. customThe flask was removed from the glovebox
  3. temperaturewhile maintaining a nitrogen atmosphere
  4. temperaturethe reaction mixture was then heated
  5. temperatureat reflux (about 82° C.)
  6. stirringwhile being vigorously stirred
  7. waitAfter about 2 h
  8. custom25 minutes, HPLC analysis of the reaction mixture
  9. customA portion of the reaction mixture (0.05 mL) was withdrawn
  10. customevaporated to dryness
  11. customto give an analytical sample for 1H NMR analysis

Sources & evidence

ORD record
ord-43a804bb1f6a489fad96103473667905
Source dataset
uspto-grants-2012_07
Patent number
US08212075B2

Reaction notes

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