3,6-Dichloropyridazine → 3-Chloro-6-(2-fluoro-4-methyl-phenyl)-pyridazine

HRID 882811Notes

Reaction equation

HRID 882811 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[F-].[K+].[F:24][C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:26]=1B(O)O>O1CCOCC1.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]>[Cl:1][C:2]1[N:3]=[N:4][C:5]([C:26]2[CH:27]=[CH:28][C:29]([CH3:31])=[CH:30][C:25]=2[F:24])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 673313,6-DichloropyridazineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 2783132(2-Fluoro-4-methylphenyl)boronic acid

Product 1

HCID 116657393-Chloro-6-(2-fluoro-4-methyl-phenyl)-pyridazine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
120 °C

Procedure

To a solution of 3,6-dichloropyridazine (2.0 g, 13.42 mmole) in 1,4-dioxane (20 ml) are added Pd2(dba)3 (0.21 g, 0.2 mmole), P(tBu)3 (0.122 g, 0.6 mmole) in 1,4-dioxane (1 ml), KF (2.57 g, 44.3 mmole) and 2-fluoro-4-methylbenzeneboronic acid (step 31.1, 2.68 g, 17.45 mmole). The resulting mixture is heated at 120° C. for 48 h. The reaction mixture is filtered through celite and washed pad with EtOAc. The filtrate is washed with H2O, dried over MgSO4 (anhydrous) and evaporated under reduced pressure to give a brown solid, which is purified by chromatography, affording the title product.

Workup

  1. filtrationThe reaction mixture is filtered through celite
  2. washwashed pad with EtOAc
  3. washThe filtrate is washed with H2O
  4. dry with materialdried over MgSO4 (anhydrous)
  5. customevaporated under reduced pressure
  6. customto give a brown solid, which
  7. customis purified by chromatography

Sources & evidence

ORD record
ord-25d77c4399fc4f3ca3ad29b581211f52
Source dataset
uspto-grants-2012_08
Patent number
US08236803B2

Reaction notes

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