Phenol → 5-Bromo-3-phenoxypyrazin-2-amine

HRID 911858Notes

Reaction equation

HRID 911858 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[C:11]1[C:12]([NH2:18])=[N:13][CH:14]=[C:15]([Br:17])[N:16]=1.C(OCC)(=O)C>C1COCC1>[Br:17][C:15]1[N:16]=[C:11]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[C:12]([NH2:18])=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 6200042-Amino-3,5-dibromopyrazine

Product 1

HCID 179560215-Bromo-3-phenoxypyrazin-2-amineYield 64.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Added sodium hydride (0.348 g, 8.70 mmol) to a solution of phenol (0.819 g, 8.70 mmol) in THF (50 mL) at 0° C. and stirred 30 minutes. Added 3,5-dibromopyrazin-2-amine (2.00 g, 7.91 mmol) in THF (10 mL). Removed the ice bath and refluxed overnight. Partitioned between ethyl acetate and water, washed with brine, dried, and concentrated. Purified by MPLC (Biotage) eluting with 5:1 hexane:ethyl acetate to afford the title compound (1.36 g, 64.6% yield) as a light yellow solid.

Workup

  1. customRemoved the ice bath
  2. temperaturerefluxed overnight
  3. customPartitioned between ethyl acetate and water
  4. washwashed with brine
  5. customdried
  6. concentrationconcentrated
  7. customPurified by MPLC (Biotage)
  8. washeluting with 5:1 hexane

Sources & evidence

ORD record
ord-c87ab2dfebb645b6b1ec43ecc4a19a33
Source dataset
uspto-grants-2011_09
Patent number
US08022223B2

Reaction notes

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