Dimethylformamide → 5-Cyanoquinoline

HRID 1861671Notes

Reaction equation

HRID 1861671 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:12][N:13](C=O)C>C1(C)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N.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>[N:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:2]([C:12]#[N:13])[C:3]=2[CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 8173215-Bromoquinoline

Product 1

HCID 47150285-Cyanoquinoline

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 0.1810 g (0.870 mmol) 10 in 5 mL DMF was added 0.0630 g (0.54 mmol) zinc cyanide and 0.0640 g (0.055 mmol) tetrakis(triphenylphosphine)palladium(0). After 66 h under argon at 80° C., the reaction mixture was cooled to room temperature, diluted with 40 mL toluene and washed with 10 mL 2N NH4H. The aqueous layer was extracted with 10 mL toluene. The combined organic layers were washed with 10 mL brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (25×130 mm silica gel, linear gradient 2-3% (10% NH4OH:MeOH):CH2Cl2) afforded 11. 1NMR (CDCl3, 400 MHz) 69.065 (dd, 1H, J=1.65, 4.21 Hz, ArH); 8.567 (d, 1H, J=8.50 Hz, ArH); 8.377 (d, 1H, J=8.50 Hz, ArH); 8.005 (dd, 1H, J=1.09, 7.22 Hz, ArH); 7.796 (dd, 1H, J=7.22, 8.59 Hz, ArH); 7.636 (dd, 1H, J=4.21, 8.51 Hz, ArH); MS (Electrospray): m/z 155.0 (M+H).

Workup

  1. washwashed with 10 mL 2N NH4H
  2. extractionThe aqueous layer was extracted with 10 mL toluene
  3. washThe combined organic layers were washed with 10 mL brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography (25×130 mm silica gel, linear gradient 2-3% (10% NH4OH:MeOH):CH2Cl2)

Sources & evidence

ORD record
ord-35b30dee244144b78629ce0548d8d08d
Source dataset
uspto-grants-2003_03
Patent number
US06534510B2

Reaction notes

Loading…