Cesium carbonate → 2-Chloro-3-(4-fluorophenyl)pyrazine

HRID 45565

Reaction equation

HRID 45565 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>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].O1CCOCC1>[Cl:8][C:7]1[C:2]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)=[N:3][CH:4]=[CH:5][N:6]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 785752,3-DichloropyrazineHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 598662582-Chloro-3-(4-fluorophenyl)pyrazineYield 55%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

First, 5.06 g of 2,3-dichloropyrazine, 5.23 g of 4-fluorophenyl boronic acid, 22.16 g of cesium carbonate, and 200 mL of dioxane were put in a three-neck flask equipped with a reflux pipe, and 0.467 g of tris(dibenzylideneacetone)dipalladium(0) (abbreviation: Pd2(dba)3) and 2.5 mL of tricyclohexylphosphine (abbreviation: Cy3P) were added thereto while the mixture was stirred under a nitrogen atmosphere, and they were reacted at 85° C. for 11 hours. After the reaction, the reaction solution was cooled down to room temperature and filtrated. A solvent of the obtained filtrate was distilled off, and the obtained residue was refined with a column chromatography using dichloromethane as a development solvent, so that 2-chloro-3-(4-fluorophenyl)pyrazine was obtained (light yellow powder, yield: 55%). A synthesis scheme of Step 1 is shown by the following (a1-1).

Workup

  1. additionwere added
  2. customthey were reacted at 85° C. for 11 hours
  3. customAfter the reaction
  4. filtrationfiltrated
  5. distillationA solvent of the obtained filtrate was distilled off

Sources & evidence

ORD record
ord-a6954906923247e688a5b7085299de23
Source dataset
uspto-grants-2013_09
Patent number
US08541574B2

Linked notes

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