Dimethylacetamide → 2-Fluoro-6-methylbenzonitrile

HRID 1466065Notes

Reaction equation

HRID 1466065 reaction equation
[F:1][C:2]1[C:3](I)=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=1.C[C:11]([N:13](C)C)=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:11]#[N:13]

Participants

5

Reactant 2

HCID 31374DimethylacetamideHCID 38363241-Fluoro-2-iodo-3-methylbenzene

Product 1

HCID 186771512-Fluoro-6-methylbenzonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A 5 L round bottom flask equipped with adapter, thermocouple and stir bar was charged with DMA (2.4 L) and degassed under vacuum and purged with N2 three times. Tetrakis was added to the mixture (35 g, 30.3 mmol) and the mixture was degassed under vacuum and purged with N2 three times. The reaction was heated to 80° C. for 30 min. 3-Fluoro-2-iodotoluene (230 g, 974 mmol) and zinc cyanide (68.7 g, 585 mmol) were added and the mixture was degassed under vacuum and purged with N2 three times. The mixture was heated to 80° C. for 16 hrs and allowed to cool to RT. The solution was added to 2.0 L aqueous solution of 1N NH4OH, which was then extracted three times with 1.5 L EtOAc, washed with 2 L brine, dried over Na2SO4, filtered, concentrated and purified by silica chromatography (PE/EA=10:1) to give the title compound.

Workup

  1. customA 5 L round bottom flask equipped with adapter
  2. customdegassed under vacuum
  3. custompurged with N2 three times
  4. customthe mixture was degassed under vacuum
  5. custompurged with N2 three times
  6. customthe mixture was degassed under vacuum
  7. custompurged with N2 three times
  8. temperatureThe mixture was heated to 80° C. for 16 hrs
  9. temperatureto cool to RT
  10. additionThe solution was added to 2.0 L aqueous solution of 1N NH4OH, which
  11. extractionwas then extracted three times with 1.5 L EtOAc
  12. washwashed with 2 L brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. custompurified by silica chromatography (PE/EA=10:1)

Sources & evidence

ORD record
ord-017957074a5e43c4827ce50a39dbff44
Source dataset
uspto-grants-2015_04
Patent number
US08999990B2

Reaction notes

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