Dimethylacetamide → 5-(Difluoromethoxy)-3-methylpicolinonitrile

HRID 627733Notes

Reaction equation

HRID 627733 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH:10]([F:12])[F:11])=[CH:4][N:3]=1.C[C:14]([N:16](C)C)=O>O.[C-]#N.[Zn+2].[C-]#N.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].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]>[F:11][CH:10]([F:12])[O:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([C:14]#[N:16])=[N:3][CH:4]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 90301367HCID 90301367, compound

Product 1

HCID 666659915-(Difluoromethoxy)-3-methylpicolinonitrileYield 49.8%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
110 °C

Procedure

A mixture of 2-chloro-5-(difluoromethoxy)-3-methylpyridine (12.4 g, 64.1 mmol), zinc cyanide (4.07 mL, 64.1 mmol), 1,1′-bis(diphenylphosphino)ferrocene (2.5 g, 4.51 mmol) and tris(dibenzylideneacetone)dipalladium(0) (2.1 g, 2.93 mmol) in DMA (50 mL) was heated to 110° C. under N2 for 18 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase obtained was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 0-70% EtOAc/hex to give 5-(difluoromethoxy)-3-methylpicolinonitrile (5.88 g, 31.9 mmol, 49.8% yield). MS m/z: 185.0 [M+H].

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic phase obtained
  3. concentrationwas concentrated under reduced pressure
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with 0-70% EtOAc/hex

Sources & evidence

ORD record
ord-794cb285561a445aa45489aaa3ecdbbb
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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