Dimethylacetamide → 4-Bromo-3,5-dimethyl-benzonitrile

HRID 2371013Notes

Reaction equation

HRID 2371013 reaction equation
[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](OS(C(F)(F)F)(=O)=O)=[CH:4][C:3]=1[CH3:17].C([C:21]#[N:22])(C)=O.CC(N(C)C)=O>CCOC(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.[Cu]I.[C-]#N.[C-]#N.[Zn+2]>[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:21]#[N:22])=[CH:4][C:3]=1[CH3:17]

Participants

8

Reactant 3

HCID 31374DimethylacetamideHCID 694302-OxopropiononitrileHCID 579788384-Bromo-3,5-dimethylphenyl trifluoromethanesulfonate

Product 1

HCID 110850704-Bromo-3,5-dimethyl-benzonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Trifluoro-methanesulfonic acid 4-bromo-3,5-dimethyl-phenyl ester (79.8 g, 0.24 mol) and AcCN (500 mL) were added to a 3 necked, 2.0 L round bottom flask equipped with mechanical stirrer, nitrogen inlet adapter, heating mantle and thermocouple. To the resulting solution were then added Pd(PPh3)4 (27.7 g, 0.024 mol), CuI (9.2 g, 0.048 mol) and Zn(CN)2 (79.8 g, 0.24 mol). The resulting mixture was stirred for 45 minutes at 50° C., DMAc (150 mL) was added and the temperature was increased to 80-88° C. and the mixture aged at this temperature overnight. The resulting mixture was cooled to ambient temperature, diluted with EtOAc (200 mL), and filtered with STAND SUPER-CEL 815520. The SUPER-CEL cake was rinsed with EtOAc (200 mL×6). The EtOAc solutions were combined and quenched with a 4:1:4 mixture of saturated NH4Cl: concentrated NH4OH:H2O (240 mL:60 mL:240 mL). The layers were separated and the organic layer was rinsed once with water (500 mL) and once with brine (500 mL), then concentrated to dryness in vacuo to yield a red thick oil. The title compound was crystallized from EtOAc (135 mL) and heptane (500 mL) to yield white-yellowish crystal.

Workup

  1. custom2.0 L round bottom flask equipped with mechanical stirrer, nitrogen inlet adapter
  2. temperatureheating mantle
  3. temperaturethe temperature was increased to 80-88° C.
  4. customaged at this temperature overnight
  5. temperatureThe resulting mixture was cooled to ambient temperature
  6. filtrationfiltered with STAND SUPER-CEL 815520
  7. washThe SUPER-CEL cake was rinsed with EtOAc (200 mL×6)
  8. customquenched with a 4:1:4 mixture of saturated NH4Cl
  9. customThe layers were separated
  10. washthe organic layer was rinsed once with water (500 mL) and once with brine (500 mL)
  11. concentrationconcentrated to dryness in vacuo
  12. customto yield a red thick oil
  13. customThe title compound was crystallized from EtOAc (135 mL) and heptane (500 mL)
  14. customto yield white-yellowish crystal

Sources & evidence

ORD record
ord-432a4f0d6c6d41988d991bdbbd61da01
Source dataset
uspto-grants-2014_04
Patent number
US08710256B2

Reaction notes

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