Ethyl Acetate → 2-Chloro-3-(3,4-dichloro-phenyl)-pyrazine

HRID 220426Notes

Reaction equation

HRID 220426 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[CH:14][C:15]=1[Cl:16].[F-].[K+].CCOC(C)=O>C1(C)C=CC=CC=1.O.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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:8][C:7]1[C:2]([C:13]2[CH:12]=[CH:11][C:10]([Cl:9])=[C:15]([Cl:16])[CH:14]=2)=[N:3][CH:4]=[CH:5][N:6]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 785752,3-DichloropyrazineHCID 522689Potassium FluorideHCID 27343303,4-Dichlorobenzeneboronic acid

Product 1

HCID 656467322-Chloro-3-(3,4-dichloro-phenyl)-pyrazineYield 23%

Reagents, catalysts & solvents 3

HCID 178420534HCID 178420534, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

Dissolve 2,3-dichloropyrazine (2.42 g, 2.03 mmol) and 3,4-dichlorobenzene boronic acid (0.406 g, 2.13 mmol) in toluene (6 mL). Add a solution of potassium fluoride (0.36 g; 6.2 mmol) in deionized water (5 mL). Add tetrakis triphenylphosphine (0.124 gm; 0.11 mmol). Reflux the reaction for 17 hr.s, cool to ambient temperature, and add EtOAc (10 mL) and water (10 mL). Separate the organic layer, re-extract the aqueous layer with EtOAc (2×40 mL), and combine the organic layers. Wash the organic solution with saturated aq NaHCO3 and brine (2×), dry over MgSO4, filter and concentrate. Purify via chromatography on silica gel eluting 0-40% ethyl acetate/hexanes to give the title preparation (0.124 g, 23% yield). MS (ES) m/z: 274, 276 (M)+.

Workup

  1. temperatureReflux
  2. customthe reaction for 17 hr
  3. customSeparate the organic layer
  4. extractionre-extract the aqueous layer with EtOAc (2×40 mL)
  5. washWash the organic solution with saturated aq NaHCO3 and brine (2×)
  6. dry with materialdry over MgSO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify via chromatography on silica gel eluting 0-40% ethyl acetate/hexanes
  10. customto give the title
  11. custompreparation (0.124 g, 23% yield)

Sources & evidence

ORD record
ord-4d307c861a1849b0966de9460f189ace
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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