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

HRID 1806106Notes

Reaction equation

HRID 1806106 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-0f944b55298a4bdf9569b1def2612c50
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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