Water → 1-(2,6-Dimethyl-4-(pyrazin-2-yloxy)phenyl)ethanone

HRID 1465530Notes

Reaction equation

HRID 1465530 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9](=[O:11])[CH3:10])=[C:4]([CH3:12])[CH:3]=1.Cl[C:14]1[CH:19]=[N:18][CH:17]=[CH:16][N:15]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.[Cu]>[CH3:12][C:4]1[CH:3]=[C:2]([O:1][C:14]2[CH:19]=[N:18][CH:17]=[CH:16][N:15]=2)[CH:7]=[C:6]([CH3:8])[C:5]=1[C:9](=[O:11])[CH3:10]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 73277ChloropyrazineHCID 40573701-(4-Hydroxy-2,6-dimethylphenyl)ethanone

Product 1

HCID 866908331-(2,6-Dimethyl-4-(pyrazin-2-yloxy)phenyl)ethanoneYield 88%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(4-hydroxy-2,6-dimethylphenyl)ethanone (4-2, 4.66 g, 28.4 mmol), 2-chloropyrazine (2.50 g, 21.8 mmol), copper (27.7 mg, 4.36 mmol), and potassium carbonate (9.05 g, 65.5 mmol) in 43.7 mL of DMF was stirred at 100° C. overnight. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4(s), concentrated under reduced pressure, and purified by column chromatography on silica gel (50% EtOAc in hexanes as eluant) to give 1-(2,6-dimethyl-4-(pyrazin-2-yloxy)phenyl)ethanone (7-1, 4.65 g) as brown oils: 1H NMR (500 MHz, CDCl3) δ 8.43 (bs, 1 H), 8.29 (bs, 1 H), 8.14 (bs, 1 H), 6.83 (s, 2 H), 2.49 (s, 3 H), 2.27 (s, 6 H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous MgSO4(s)
  4. concentrationconcentrated under reduced pressure
  5. custompurified by column chromatography on silica gel (50% EtOAc in hexanes as eluant)

Sources & evidence

ORD record
ord-c979417c5159455b829bfa571419b207
Source dataset
uspto-grants-2015_04
Patent number
US08999983B2

Reaction notes

Loading…