Dimethylformamide → 2-Fluoro-5-isopropylnicotinonitrile

HRID 2070932Notes

Reaction equation

HRID 2070932 reaction equation
[F:1][C:2]1[C:7](I)=[CH:6][C:5]([CH:9]([CH3:11])[CH3:10])=[CH:4][N:3]=1.[CH3:12][N:13](C=O)C>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[N:3]=[CH:4][C:5]([CH:9]([CH3:11])[CH3:10])=[CH:6][C:7]=1[C:12]#[N:13]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 686713802-Fluoro-3-iodo-5-isopropylpyridine

Product 1

HCID 686699662-Fluoro-5-isopropylnicotinonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-fluoro-3-iodo-5-isopropylpyridine and 485 mg (4.13 mmol) of Zn(CN)2 in 15 mL of DMF (degassed) was added 360 mg (0.312 mmol) of Pd(PPh3)4. The mixture was heated at 80° C. under Ar for 19 h. The mixture was diluted with EtOAc, and the organic layer was washed with 10% NH4OH (2×10 mL), H2O (3×), and brine. The organic layer was dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (5% Et2O/hexanes) provided 384 mg of pure 2-fluoro-5-isopropylnicotinonitrile as a yellow liquid.

Workup

  1. washthe organic layer was washed with 10% NH4OH (2×10 mL), H2O (3×), and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash silica gel chromatography (5% Et2O/hexanes)

Sources & evidence

ORD record
ord-5e8e5e5ec9a9429bbc190360b93d58f4
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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