Phenol → HCID 89782016, compound

HRID 1055865Notes

Reaction equation

HRID 1055865 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[N:13]=[C:14](Cl)[C:15]([NH2:21])=[N:16]2>CN(C=O)C>[Br:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[N:13]=[C:14]([O:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:15]([NH2:21])=[N:16]2

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 89781995HCID 89781995, compound

Product 1

HCID 89782016HCID 89782016, compoundYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a slurry of NaH (60% dispersion in mineral oil; 0.193 g, 4.84 mmol) in 5 mL DMF at 0° C. under N2 was added phenol (0.455 g, 4.84 mmol). Gas evolution was observed. The reaction was warmed to RT. After 5 min, 5-bromo-3-chloroquinoxalin-2-amine (0.250 g, 0.967 mmol) was added, and the reaction was sealed and stirred overnight. The reaction was partitioned between saturated aq. NH4Cl and EtOAc. The organic layer was sequentially washed with water (1×), and saturated aq. NaCl (1×), and then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and adsorbed onto 2 g silica gel and dried. The material was purified by silica gel chromatography using 0-60% EtOAc/hexane. The product-containing fractions were concentrated to afford 5-bromo-3-phenoxyquinoxalin-2-amine (0.209 g, 0.661 mmol, 68% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.55 (1H, dt, J=7.6, 0.7 Hz), 7.37-7.51 (7H, m), 7.26-7.35 (2H, m). m/z (ESI, +ve) 316.0 (M+H)+.

Workup

  1. customthe reaction was sealed
  2. customThe reaction was partitioned between saturated aq. NH4Cl and EtOAc
  3. washThe organic layer was sequentially washed with water (1×), and saturated aq. NaCl (1×)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe material was treated with DCM
  8. customdried
  9. customThe material was purified by silica gel chromatography
  10. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-621dac5281fe4b65be6b8e25b4ea3d6e
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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