Water → 3-(Trifluoromethyl)pyridine-2-carbonitrile

HRID 2054328Notes

Reaction equation

HRID 2054328 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][N:3]=1.O.[Cl-].[NH4+].[OH-].[NH4+].[CH3:17][N:18](C=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].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].CCOC(C)=O>[C:17]([C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][N:3]=1)#[N:18]

Participants

10

Reactant 5

HCID 962Water2×HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 5898332-Chloro-3-(trifluoromethyl)pyridine

Product 1

HCID 223215743-(Trifluoromethyl)pyridine-2-carbonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 2-chloro-3-trifluoromethylpyridine (36.2 g, 0.2 moles) in DMF (350 mL) at room temperature. Add water (3.5 mL) and zinc cyanide (14 g, 0.12 moles) to the reaction mixture and degas with nitrogen for 15 minutes. Add catalyst Pd2(dba)3 (5.5 g, 3 mol %) and ligand DPPF (6.5 g, 6 mol %) to the mixture and then heat at 120° C. with stirring for 1 hour. Cool the reaction mixture in an ice bath and then add saturated ammonium chloride (200 mL), 28% ammonium hydroxide (50 mL) and water (50 mL). Stir the resulting reaction mixture in the ice bath for 1 hour and then dilute it EtOAc (300 mL). Separate the organic layer, extract the aqueous layer with EtOAc (3×300 mL), wash the combined organic layers with brine (2×200 mL) and dry (MgSO4). Filter the dried extract and concentrate under vacuum to afford crude product as dark brown oil. Purify the crude product by vacuum distillation to afford pure product as colorless oil.

Workup

  1. temperatureCool the reaction mixture in an ice bath
  2. stirringStir
  3. customSeparate the organic layer
  4. extractionextract the aqueous layer with EtOAc (3×300 mL)
  5. washwash the combined organic layers with brine (2×200 mL)
  6. dry with materialdry (MgSO4)
  7. filtrationFilter the dried
  8. extractionextract
  9. concentrationconcentrate under vacuum
  10. customto afford crude product as dark brown oil
  11. customPurify the crude product
  12. distillationby vacuum distillation
  13. customto afford pure product as colorless oil

Sources & evidence

ORD record
ord-ef8d7a64e6e24f98b855605f2cf2c94e
Source dataset
uspto-grants-2008_02
Patent number
US07329664B2

Reaction notes

Loading…