2,5-Dichloro-4-(2,2,2-trifluoroethoxy)pyridine → 5-Chloro-4-(2,2,2-trifluoroethoxy)picolinonitrile

HRID 1480071Notes

Reaction equation

HRID 1480071 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[C:5]([Cl:14])=[CH:4][N:3]=1.[C:15]([Zn]C#N)#[N:16]>CN(C=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:14][C:5]1[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:7][C:2]([C:15]#[N:16])=[N:3][CH:4]=1

Participants

6

Reactant 2

HCID 902044262,5-Dichloro-4-(2,2,2-trifluoroethoxy)pyridineHCID 178514179HCID 178514179, compound

Product 1

HCID 902038885-Chloro-4-(2,2,2-trifluoroethoxy)picolinonitrileYield 73%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2,5-dichloro-4-(2,2,2-trifluoroethoxy)-pyridine (Example 24a, 1.48 g, 6.02 mmol) in dry DMF (30 mL) under an argon atmosphere was added dicyanozinc (707 mg, 6.02 mmol), 1,1′-bis(diphenylphosphino)ferrocene (267 mg, 481 μmol) and tris(dibenzylideneacetone) dipalladium(0) (275 mg, 301 μmol). The reaction was stirred at 100° C. for 18 h, cooled and filtered through a pad of celite. The filtrate was diluted with ethylacetate and extracted with a 1.0M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous solution was back-extracted with ethylacetate. The organic phases were combined, dried over sodium sulfate and evaporated down to dryness. The residue was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient to yield the title compound (1.04 g, 73%) as a yellow oil. MS (ESI, m/z): 237.3 (M+H+).

Workup

  1. temperaturecooled
  2. filtrationfiltered through a pad of celite
  3. additionThe filtrate was diluted with ethylacetate
  4. extractionextracted with a 1.0M aqueous solution of sodium bicarbonate
  5. customThe organic phase was collected
  6. extractionthe aqueous solution was back-extracted with ethylacetate
  7. dry with materialdried over sodium sulfate
  8. customevaporated down to dryness
  9. customThe residue was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient

Sources & evidence

ORD record
ord-77bd4f0ba49e42bf9adadfbb4447ce74
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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