Potassium Carbonate → Ethyl 6-isobutyl-3-methylpyrazine-2-carboxylate

HRID 869724Notes

Reaction equation

HRID 869724 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:5]([CH3:13])=[N:4][CH:3]=1.[CH2:14](B(O)O)[CH:15]([CH3:17])[CH3:16].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:14]([C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:5]([CH3:13])=[N:4][CH:3]=1)[CH:15]([CH3:17])[CH3:16]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2734395(2-Methylpropyl)boronic acidHCID 87384166Ethyl 6-chloro-3-methylpyrazine-2-carboxylate

Product 1

HCID 67395659Ethyl 6-isobutyl-3-methylpyrazine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of ethyl 6-chloro-3-methylpyrazine-2-carboxylate (1.94 g, 9.67 mmol), isobutylboronic acid (1.97 g, 19.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(212 mg, 0.290 mmol), and potassium carbonate (2.67 g, 19.3 mmol) in 1,4-dioxane (30 mL) was heated at 100° C. for 4.5 h. After being cooled to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtrated through celite with ethyl acetate. The filtrate was combined and concentrated in vacuo. The residue was diluted ethyl acetate, and washed with saturated aqueous sodium bicarbonate and saturated brine, dried over sodium bicarbonate, filtrated and concentrated in vacuo. The residue was dissolved to dichloromethane, and the insoluble materials were filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:1) to give ethyl 6-isobutyl-3-methylpyrazine-2-carboxylate. MS (APCI): m/z 223 (M+H).

Workup

  1. temperatureAfter being cooled to ambient temperature
  2. filtrationfiltrated through celite with ethyl acetate
  3. concentrationconcentrated in vacuo
  4. washwashed with saturated aqueous sodium bicarbonate and saturated brine
  5. dry with materialdried over sodium bicarbonate
  6. filtrationfiltrated
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved to dichloromethane
  9. filtrationthe insoluble materials were filtered off
  10. concentrationThe filtrate was concentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:1)

Sources & evidence

ORD record
ord-cb42aecc7f1b48e6836d3092f75b0c14
Source dataset
uspto-grants-2015_03
Patent number
US08969376B2

Reaction notes

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