Potassium Carbonate → 3-(6-chloropyridazin-3-yl)benzonitrile

HRID 655239Notes

Reaction equation

HRID 655239 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].[Cl:12][C:13]1[N:14]=[N:15][C:16](Cl)=[CH:17][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:12][C:13]1[N:14]=[N:15][C:16]([C:7]2[CH:8]=[C:3]([CH:4]=[CH:5][CH:6]=2)[C:1]#[N:2])=[CH:17][CH:18]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 673313,6-DichloropyridazineHCID 27343253-Cyanophenylboronic acid

Product 1

HCID 135734663-(6-chloropyridazin-3-yl)benzonitrileYield 45.5%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Nitrogen gas was bubbled through a mixture of 3-cyanophenyl boronic acid (90.0 g, 612 mmol), 3,6-dichloropyridazine (1.2 eq, 109.4 g, 735 mmol), potassium carbonate (3.0 eq, 253.5 g, 1.836 mol) in 1,4-dioxane (900 mL) and water (360 mL) for 15 minutes. After such time dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.06 eq, 26.8 g, 36.7 mmol) was added. Nitrogen bubbled through for further 10 mins then the mixture was heated to 90° C. for 3 hours. The reaction was cooled and the most of the 1,4-dioxane was removed under vacuo. The mixture taken up in dichloromethane and washed with water three times. The organic layer was concentrated and the residue was purified by column chromatography to return the title compound (60 g, 45.5% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ 8.58˜8.59 (m, 1H), 8.44˜8.52 (m, 2H), 8.09˜8.12 (d, 1H), 8.02˜8.05 (d, 1H), 7.76˜7.81 (m, 1H); MS (m/z) 216.1 (M++1).

Workup

  1. customNitrogen bubbled through for further 10 mins
  2. temperatureThe reaction was cooled
  3. customthe most of the 1,4-dioxane was removed under vacuo
  4. washwashed with water three times
  5. concentrationThe organic layer was concentrated
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-192a4bf1cc084744a5a4009a673de231
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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