N,N-Dimethylformamide--water (1/1) → 6-Acetyl-5-trifluoromethyl-nicotinonitrile

HRID 545089Notes

Reaction equation

HRID 545089 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:11]([F:14])([F:13])[F:12])[C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=1.[CH3:15][N:16](C=O)C.O>[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:8]([C:5]1[C:4]([C:11]([F:14])([F:13])[F:12])=[CH:3][C:2]([C:15]#[N:16])=[CH:7][N:6]=1)(=[O:10])[CH3:9]

Participants

6

Reactant 2

HCID 21962138N,N-Dimethylformamide--water (1/1)HCID 586455621-(5-Bromo-3-(trifluoromethyl)pyridin-2-yl)ethanone

Product 1

HCID 671902526-Acetyl-5-trifluoromethyl-nicotinonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

Dissolve 1-(5-bromo-3-(trifluoromethyl)pyridin-2-yl)ethanone (2.67 g, 0.01 mol) in anhydrous DMF/H2O (30.0:0.3 mL) and degas the resulting solution with N2 for 10 minutes. Add Zn(CN)2 (1.17 g, 0.01 mol), Pd2(dba)3 (229 mg, 2.5 mol %) and DPPF (270 mg, 5 mol %). Purge the mixture with N2 for another 10 minutes and heat at 120° C. under N2 atmosphere for 45 minutes. Cool the reaction mixture to room temperature, dilute with water, extract with EtOAc (3×75 mL) and dry (MgSO4). Filter the dried extract and concentrate under vacuum to afford the crude product, which is purified by column chromatography to afford the title product as a yellow solid.

Workup

  1. customdegas the resulting solution with N2 for 10 minutes
  2. customPurge the mixture with N2 for another 10 minutes
  3. temperatureCool the reaction mixture to room temperature
  4. additiondilute with water
  5. extractionextract with EtOAc (3×75 mL)
  6. dry with materialdry (MgSO4)
  7. filtrationFilter the dried
  8. extractionextract
  9. concentrationconcentrate under vacuum
  10. customto afford the crude product, which
  11. customis purified by column chromatography

Sources & evidence

ORD record
ord-c72bae1c6ac94d2d8550f12b05f9a01b
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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