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

HRID 335179Notes

Reaction equation

HRID 335179 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-3e574ba7a29c4ba497c42a3d72ab1c9b
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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