Potassium Carbonate → 6-(4-Bromo-3-formyl-phenoxy)-2-(2,2-difluoro-ethoxy)-nicotinonitrile

HRID 1664430Notes

Reaction equation

HRID 1664430 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH:12]([F:14])[F:13])[N:3]=1.[Br:15][C:16]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:17]=1[CH:18]=[O:19].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.O>[Br:15][C:16]1[CH:23]=[CH:22][C:21]([O:24][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH:12]([F:14])[F:13])[N:3]=2)=[CH:20][C:17]=1[CH:18]=[O:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 3871792-Bromo-5-hydroxybenzaldehydeHCID 866364586-Chloro-2-(2,2-difluoro-ethoxy)-nicotinonitrile

Product 1

HCID 866364596-(4-Bromo-3-formyl-phenoxy)-2-(2,2-difluoro-ethoxy)-nicotinonitrileYield 90.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-chloro-2-(2,2-difluoro-ethoxy)-nicotinonitrile (5.01 g, 22.9 mmol), 2-bromo-5-hydroxy-benzaldehyde (3.84 g, 19.1 mmol) and K2CO3 (5.3 g, 38 mmol) in dimethylformamide (30 mL) was heated to 110° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with H2O (800 mL) and extracted with ethyl acetate (4×800 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash column chromatography (20% ethyl acetate/hexanes) to give the title compound as a white solid (6.62 g, 90%)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (4×800 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bfa7da4959ec4f46aabb84c63df0f3d8
Source dataset
uspto-grants-2011_10
Patent number
US08039450B2

Reaction notes

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