Water → 4-Amino-2-chloro-3-methylbenzonitrile

HRID 1157664

Reaction equation

HRID 1157664 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8]C(=O)C)=[C:4]([CH3:12])[C:3]=1[Cl:13].[Cu](C#N)[C:15]#[N:16].C(N)CN.O>CN1CCCC1=O.[Cu](I)I>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]#[N:16])=[C:3]([Cl:13])[C:4]=1[CH3:12]

Participants

7

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 86376N-(4-Bromo-3-chloro-2-methylphenyl)acetamideHCID 178418260HCID 178418260, compound

Product 1

HCID 218754134-Amino-2-chloro-3-methylbenzonitrileYield 79%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Dissolve N-(4-bromo-3-chloro-2-methyl-phenyl)-acetamide (10 g, 38 mmol) in N-methylpyrrolidinone (60 mL) and sparge with nitrogen. Add copper cyanide (10.2 g, 114 mol) and copper iodide (21.8 g, 114 mol) and stir under nitrogen at 130° C. for 72 h. Cool the reaction and add ethylene diamine (100 mL), along with water (300 mL). Extract the reaction mixture with EtOAc. Separate and dry the organic portion over Na2SO4, filter, and concentrate. Dissolve the resulting residue in 1:1 EtOH/concentrated HCl. Stir at reflux temperature for 30 min, cool and concentrate to half of the volume. Add water (500 mL) and filter. Rinse the filter cake with water and isolate 5.0 g (79%) of the title compound as a white solid. MS: MS (ESI−): 207 (M−1)−. MS (ESI+): 209 (M+1)+.

Workup

  1. customsparge with nitrogen
  2. temperatureCool
  3. customthe reaction
  4. extractionExtract the reaction mixture with EtOAc
  5. customSeparate
  6. dry with materialdry the organic portion over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. dissolutionDissolve the resulting residue in 1:1 EtOH/concentrated HCl
  10. temperatureat reflux temperature for 30 min
  11. temperaturecool
  12. concentrationconcentrate to half of the volume
  13. filtrationAdd water (500 mL) and filter
  14. washRinse the filter cake with water

Sources & evidence

ORD record
ord-b0401f6634cf4850a8d0e68bbd35d061
Source dataset
uspto-grants-2010_10
Patent number
US07807691B2

Linked notes

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