Hydrochloric Acid → Methyl 6-amino-3-methoxy-2-pyrazinecarboxylate

HRID 1005731Notes

Reaction equation

HRID 1005731 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][CH3:13])=[N:4][CH:3]=1.C(=[NH:27])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.O1CCCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(Cl)(Cl)Cl>[NH2:27][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][CH3:13])=[N:4][CH:3]=1

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136809Benzophenone imineHCID 22248028Methyl 6-bromo-3-methoxypyrazine-2-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 22662843Methyl 6-amino-3-methoxy-2-pyrazinecarboxylateYield 43.1%

Reagents, catalysts & solvents 6

HCID 634876Binap, (A+-)-CatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

In a nitrogen atmosphere, 11.38 g of methyl 6-bromo-3-methoxy-2-pyrazinecarboxylate is dissolved in 227 mL of toluene. To the solution are successively added 10.32 g of benzophenone-imine, 0.42 g of tris(dibenzylideneacetone) dipalladium, 0.86 g of (s)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 6.20 g of sodium t-butoxide. The resulting mixture is stirred at 80° C. for one hour. The reaction mixture is cooled and filtered. The filtrate is purified by column chromatography (eluent: toluene:ethyl acetate=20:1). The oily product thus obtained is dissolved in 140 mL of tetrahydrofuran, 7 mL of 2 mol/mL hydrochloric acid is added thereto and the resulting solution is stirred at ambient temperature for 15 minutes. A mixture of 200 mL of chloroform and 50 mL of water is added to the resulting reaction mixture, and alkalified with 1 mol/mL of sodium hydroxide, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is purified by column chromatography (eluent: toluene:ethyl acetate 1:1) to obtain 3.64 g of methyl 6-amino-3-methoxy-2-pyrazinecarboxylate.

Workup

  1. temperatureThe reaction mixture is cooled
  2. filtrationfiltered
  3. customThe filtrate is purified by column chromatography (eluent: toluene:ethyl acetate=20:1)
  4. customThe oily product thus obtained
  5. stirringthe resulting solution is stirred at ambient temperature for 15 minutes
  6. additionis added to the resulting reaction mixture
  7. customthe organic layer is separated
  8. washThe organic layer is washed with saturated aqueous solution of sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationthe solvent is distilled off under reduced pressure
  11. customThe residue thus obtained
  12. customis purified by column chromatography (eluent: toluene:ethyl acetate 1:1)

Sources & evidence

ORD record
ord-aa80cebfd753424aa3216e70b8cd2f15
Source dataset
uspto-grants-2004_09
Patent number
US06787544B2

Reaction notes

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