Hydrochloric Acid → 2-Chloro-5-(methylsulfanyl)pyrazine

HRID 1964659Notes

Reaction equation

HRID 1964659 reaction equation
N([O-])=O.[Na+].[ClH:5].[CH3:6][S:7][C:8]1[N:9]=[CH:10][C:11](N)=[N:12][CH:13]=1>O>[Cl:5][C:11]1[CH:10]=[N:9][C:8]([S:7][CH3:6])=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 218972225-(Methylthio)pyrazin-2-amineHCID 23668193Sodium Nitrite

Product 1

HCID 866495722-Chloro-5-(methylsulfanyl)pyrazineYield 26%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Sodium nitrite (50.9 g, 0.74 mol) was dissolved in water (150 mL), followed by dropwise addition into a 5N aqueous hydrochloric acid solution (1.0 L) at 0° C. over 1 hour. Subsequently, 5-(methylsulfanyl)pyrazine-2-amine (40.4 g, 0.28 mol) synthesized in Example (97a) was added at 0° C. over 40 minutes, and stirring was carried out at 0° C. for 1 hour. The reaction solution was brought back to room temperature, and water (500 mL) was added, followed by extraction with ethyl acetate (1.0 L). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-20%) to afford the desired compound (11.9 g, yield 26%) as a white solid.

Workup

  1. customwas brought back to room temperature
  2. extractionfollowed by extraction with ethyl acetate (1.0 L)
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=10%-20%)

Sources & evidence

ORD record
ord-e3213cb947234e4096834b0a2c8402b9
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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