Dimethylformamide → 6,8-Difluoro-4-quinolinecarbonitrile

HRID 1094640Notes

Reaction equation

HRID 1094640 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([F:13])[CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:14][N:15](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[C:7]([F:13])[CH:8]=1)[N:5]=[CH:4][CH:3]=[C:2]2[C:14]#[N:15]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 27365024-chloro-6,8-difluoroquinoline

Product 1

HCID 666378056,8-Difluoro-4-quinolinecarbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A mixture of 4-chloro-6,8-difluoroquinoline (APOLLO) (1000 mg, 5.01 mmol), zinc cyanide (1180 mg, 10.0 mmol) and palladium (0) tetrakis(triphenylphosphine)(579 mg, 0.501 mmol) in dry DMF (15 ml) was treated at room temperature with stirring for 12 hours. Then, the reaction was quenched with saturated aqueous sodium bicarbonate solution and ethyl acetate. The organic layer was separated and the crude product was purified by column chromatography on silica gel (ca. 250 g) with hexane-ethyl acetate (3:1) to give the title compound (787 mg, yellow solid). 1H NMR (270 MHz, CDCl3) 5 ppm 7.37-7.50 (1H, m), 7.65-7.75 (1H, m), 7.83-7.90 (1H, m), 9.05-9.10 (1H, m).

Workup

  1. additionwas treated at room temperature
  2. customThen, the reaction was quenched with saturated aqueous sodium bicarbonate solution and ethyl acetate
  3. customThe organic layer was separated
  4. customthe crude product was purified by column chromatography on silica gel (ca. 250 g) with hexane-ethyl acetate (3:1)

Sources & evidence

ORD record
ord-8518340b0c6e4ecfb502d84ddf976874
Source dataset
uspto-grants-2012_03
Patent number
US08134004B2

Reaction notes

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