Dimethylacetamide → 4-(4-Aminobenzoyl)benzonitrile

HRID 926470

Reaction equation

HRID 926470 reaction equation
CN1[C:6]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)=[O:8])=[CH:5]N=C1.C1(P(C2CCCCC2)[C:25]2C=CC=C[C:26]=2[C:31]2[C:36](C(C)C)=CC(C(C)C)=C[C:32]=2C(C)C)CCCCC1.CC([N:55](C)C)=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Zn]>[NH2:15][C:12]1[CH:11]=[CH:10][C:9]([C:7]([C:6]2[CH:5]=[CH:36][C:31]([C:32]#[N:55])=[CH:26][CH:25]=2)=[O:8])=[CH:14][CH:13]=1

Participants

8

Reactant 3

HCID 31374DimethylacetamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86715600(1-Methyl-1H-imidazol-5-yl)(4-nitrophenyl)methanone2×

Product 1

HCID 198022084-(4-Aminobenzoyl)benzonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture containing (4-aminophenyl)(4-chlorophenyl)methanone (2.5 g, 11 mmol, Intermediate 16: step b), zinc cyanide (1.65 g, 14.0 mmol), tris(dibenzylideneacetone)dipalladium (692 mg, 0.755 mmol), zinc powder (141 mg, 2.16 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos, 371 mg, 0.755 mmol), and dimethylacetamide (54 mL, sparged with nitrogen for 45 minutes) was heated to 120° C. After 2 hours, the flask was allowed to cool to 23° C. The mixture was diluted with ethyl acetate (150 mL) and then filtered through Celite®. The filtrate was washed with saturated aqueous sodium chloride solution (2×100 mL). The organic phase was dried over sodium sulfate and then filtered. Silica gel (8 g) was added to the filtrate and the solvent was removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with dichloromethane initially, grading to 5% methanol-dichloromethane provided the title compound as a solid.

Workup

  1. temperatureto cool to 23° C
  2. filtrationfiltered through Celite®
  3. washThe filtrate was washed with saturated aqueous sodium chloride solution (2×100 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. additionSilica gel (8 g) was added to the filtrate
  7. customthe solvent was removed by rotary evaporation
  8. customto afford a free-flowing powder
  9. customThe powder was loaded onto a column of silica gel for purification
  10. washElution with dichloromethane initially

Sources & evidence

ORD record
ord-981720d70fbb48f2848e2d08a4c622fd
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Linked notes

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