3-Chloro-2,5-dimethylpyrazine → 2,5-Dimethyl-3-phenylpyrazine

HRID 1795383Notes

Reaction equation

HRID 1795383 reaction equation
[C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:10]1[C:11]([CH3:17])=[N:12][CH:13]=[C:14]([CH3:16])[N:15]=1>C1COCC1>[CH3:17][C:11]1[C:10]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:15][C:14]([CH3:16])=[CH:13][N:12]=1

Participants

4

Reactant 2

HCID 667713-Chloro-2,5-dimethylpyrazineHCID 178418255HCID 178418255, compound

Product 1

HCID 136429202,5-Dimethyl-3-phenylpyrazineYield 64.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of phenylmagnesium bromide (1M in THF, 5.6 mL, 5.6 mmol) is added to a solution of 3-chloro-2,5-dimethylpyrazine (346 mg, 2.42 mmol) and Fe(acac)3 (43 mg, 0.12 mmol) in THF (10 mL) at −30° C. After stirring for 30 min at that temperature, the reaction is quenched with brine, the aqueous layer is extracted with Et2O, the combined organic phases are dried over Na2SO4 and evaporated, and the residue is purified by flash chromatography (hexane/ethyl acetate, 10:1). After eluting a first fraction containing biphenyl (212 mg), one obtains 2,5-dimethyl-3-phenylpyrazine as a pale yellow syrup (287 mg, 64%). 1H NMR (300 MHz, CD2Cl2) δ 8.31 (s, 1H), 7.55–7.59 (m, 2H), 7.43–7.51 (m, 3H), 2.55 (s, 3H), 2.54 (s, 3H). 13C NMR (75 MHz, CD2Cl2) δ 152.7, 150.6, 148.4, 142.1, 139.5, 129.3, 128.7, 128.6, 22.7, 21.2.

Workup

  1. customthe reaction is quenched with brine
  2. extractionthe aqueous layer is extracted with Et2O
  3. dry with materialthe combined organic phases are dried over Na2SO4
  4. customevaporated
  5. customthe residue is purified by flash chromatography (hexane/ethyl acetate, 10:1)
  6. washAfter eluting a first fraction
  7. additioncontaining biphenyl (212 mg), one

Sources & evidence

ORD record
ord-af417605eafc4f64b6c1d1a370bd2027
Source dataset
uspto-grants-2006_04
Patent number
US07026478B2

Reaction notes

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