Cesium carbonate → 1-{4-((5-Methoxypyridin-2-yl)oxy)-2,6-dimethylphenyl}ethanone

HRID 1465559Notes

Reaction equation

HRID 1465559 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][N:3]=1.[OH:10][C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([C:18](=[O:20])[CH3:19])=[C:13]([CH3:21])[CH:12]=1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Cu](I)I.O>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([O:10][C:11]2[CH:12]=[C:13]([CH3:21])[C:14]([C:18](=[O:20])[CH3:19])=[C:15]([CH3:17])[CH:16]=2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 40573701-(4-Hydroxy-2,6-dimethylphenyl)ethanoneHCID 111481512-Bromo-5-methoxypyridine

Product 1

HCID 866908621-{4-((5-Methoxypyridin-2-yl)oxy)-2,6-dimethylphenyl}ethanoneYield 107%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-bromo-5-methoxypyridine (18-1, 1.03 g, 5.46 mmol), 1-(4-hydroxy-2,6-dimethylphenyl)ethanone (4-2, 0.80 g, 4.89 mmol), N,N-dimethylglycine HCl salt (0.28 g, 1.95 mmol), copper iodide (0.24 g, 1.24 mmol), and cesium carbonate (3.57 g, 10.96 mmol) in dioxane (10 mL) was heated at 120° C. for 4.0 h. The reaction mixture was cooled to room temperature, added with water, and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated to give 1-{4-((5-methoxypyridin-2-yl)oxy)-2,6-dimethylphenyl}ethanone (18-2, 1.42 g) as a yellow oil in 96% yield, which was used directly for the next step without further purification.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-213196f336134868a8f83dc613ba295c
Source dataset
uspto-grants-2015_04
Patent number
US08999983B2

Reaction notes

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