Dimethylformamide → 6-Acetyl-5-trifluoromethyl-nicotinonitrile

HRID 545075Notes

Reaction equation

HRID 545075 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.[Cl-].[NH4+].[OH-].[NH4+].[CH3:19][N:20](C=O)C>O.[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].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:19]#[N:20])=[CH:7][N:6]=1)(=[O:10])[CH3:9]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 586455621-(5-Bromo-3-(trifluoromethyl)pyridin-2-yl)ethanone

Product 1

HCID 671902526-Acetyl-5-trifluoromethyl-nicotinonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×

Procedure

Heat a solution of 1-(5-bromo-3-trifluoromethyl-pyridin-2-yl)-ethanone (268 mg, 1.0 mmol), zinc cyanide (75 mg, 0.63 mmol), pd2(dba)3 (30 mg), and DPPF (35 mg) in DMF (3 mL) and water (0.03 mL), under a nitrogen atmosphere, at 120° C. for 1 hour. Cool the reaction to 0° C. and add a solution of saturated ammonium chloride solution (2 mL), water (2 mL) and concentrated ammonium hydroxide (0.5 mL) and stir for 1 hour. Extract the mixture with ethyl acetate (3×20 mL) and wash the combined organics with brine (50 mL). Dry the organic extract over MgSO4 and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with a 9:1 mixture of hexane:ether to give the title compound.

Workup

  1. temperatureCool
  2. customthe reaction to 0° C.
  3. extractionExtract the mixture with ethyl acetate (3×20 mL)
  4. washwash the combined organics with brine (50 mL)
  5. customDry the
  6. extractionorganic extract over MgSO4
  7. customremove the solvent under reduced pressure
  8. customPurify the residue by flash chromatography
  9. washeluting with a 9:1 mixture of hexane

Sources & evidence

ORD record
ord-e208a2f3aa8c4ae9a315254d1fb6cdb4
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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