Hydrochloric Acid → 3,5,6-Trichloro-pyrazine-2-carboxylic acid methyl ester

HRID 2066869Notes

Reaction equation

HRID 2066869 reaction equation
N[C:2]1[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([Cl:8])[N:7]=1.C(ON=O)CC(C)C.[ClH:22]>C(#N)C.O>[CH3:13][O:12][C:10]([C:3]1[C:2]([Cl:22])=[N:7][C:6]([Cl:8])=[C:5]([Cl:9])[N:4]=1)=[O:11]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 73828Methyl 3-amino-5,6-dichloropyrazine-2-carboxylate

Product 1

HCID 152582053,5,6-Trichloro-pyrazine-2-carboxylic acid methyl esterYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

Methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate (2.6 g, 11.8 mmol), CuCl2 (2.37 g, 17.6 mmol) and iso-amylnitrite (2.07 g, 17.7 mmol) were combined in 100 mL of acetonitrile and heated at 65° C. for 18 h. The solution was cooled, acidified with 2N HCl (50 mL), diluted with water (100 mL), and extracted with DCM (3×30 mL). The combined extracts were dried, concentrated and the residue was purified by flash chromatography (eluent: 10 to 50% EtOAc+0.1% triethylamine in hexane) to afford 56a (1.21 g, 42% yield).

Workup

  1. temperatureThe solution was cooled
  2. extractionextracted with DCM (3×30 mL)
  3. customThe combined extracts were dried
  4. concentrationconcentrated
  5. customthe residue was purified by flash chromatography (eluent: 10 to 50% EtOAc+0.1% triethylamine in hexane)

Sources & evidence

ORD record
ord-e9533698c3f345a183402a2dce8928eb
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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