Sodium Carbonate → 2-[4-(Trifluoromethyl)phenyl]pyrazine

HRID 1942307Notes

Reaction equation

HRID 1942307 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.[F:8][C:9]([F:20])([F:19])[C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[Pd+2]>[F:8][C:9]([F:20])([F:19])[C:10]1[CH:15]=[CH:14][C:13]([C:2]2[CH:7]=[N:6][CH:5]=[CH:4][N:3]=2)=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 73277ChloropyrazineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 50458142-[4-(Trifluoromethyl)phenyl]pyrazine

Reagents, catalysts & solvents 2

HCID 178478644HCID 178478644, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of chloropyrazine (10, 0.087 mol), 4-(trifluoromethyl)phenylboronic acid (21 g), palladium(diphenylphosphino)ferrocene dichloride (3.5 g, 5 mol %) and sodium carbonate (100mL, 2M) in dioxane (200 mL) was degassed (×3) via Firestone valve. The mixture was heated under reflux for 1 h. Dioxane was removed in vacuo. The residue was dispersed between ethyl acetate and water and the organic phase was washed with brine, dried (MgSO4) and evaporated. The black residue was dry-loaded onto silica and purified by elution with 5-25% ethyl acetate in iso-hexane. This afforded the product as white crystals. 1H NMR (400 MHz, CDCl3): δ 7.78 (2H, d, J 8.2), 8.15 (2H, d, J 8.2), 8.59 (1H, d, J 2.5), 8.68 (1H, t, J 2.0), 9.08 (1H, d, J 1.4).

Workup

  1. customwas degassed (×3) via Firestone valve
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 1 h
  4. customDioxane was removed in vacuo
  5. additionThe residue was dispersed between ethyl acetate and water
  6. washthe organic phase was washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. custompurified by elution with 5-25% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-78040d2a91b2469fad6c6e7e846e8914
Source dataset
uspto-grants-2013_03
Patent number
US08389547B2

Reaction notes

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