Potassium Carbonate → 3-(2-Chloro-4-cyanophenoxy)-5-(4-cyanophenoxy)benzoic acid ethyl ester

HRID 1024757Notes

Reaction equation

HRID 1024757 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[C:9]([OH:11])[CH:8]=[C:7]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)[CH:6]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Cl:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1F)[C:32]#[N:33]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:6]=[C:7]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)[CH:8]=[C:9]([O:11][C:36]2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][C:29]=2[Cl:28])[CH:10]=1)[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1455253-Chloro-4-fluorobenzonitrileHCID 668184083-(4-Cyanophenoxy)-5-hydroxy benzoic acid ethyl ester

Product 1

HCID 668185973-(2-Chloro-4-cyanophenoxy)-5-(4-cyanophenoxy)benzoic acid ethyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 1.2 g (4.23 mmol) of 3-(4-cyano-phenoxy)-5-hydroxy-benzoic acid ethyl ester, dissolved in 10 ml of DMF, potassium carbonate 1.17 g (8.46 mmol) was added and stirred for 30 min at RT. 1.31 g (8.46 mmol) of 3-chloro-4-fluoro-benzonitrile, dissolved in 5 ml of DMF, was added dropwise to the reaction mixture during 15 min and final contents were stirred at 80° C. overnight. The reaction mixture was concentrated, residue was dissolved in 200 ml of ethyl acetate and partitioned with water. The organic layer was washed with brine followed by of water. Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude product was subjected to column chromatography, using silica-gel and eluted with hexane:ethyl acetate (8:2) to afford 1.4 g of pure product. 1H NMR (DMSO-d6): δ 1.3 (3H, t), 4.3 (2H, q), 7.2-7.36 (4H, m), 7.44 (2H, dd), 7.88 (3H, m), 8.26 (1H, d).

Workup

  1. additionwas added dropwise to the reaction mixture during 15 min
  2. stirringfinal contents were stirred at 80° C. overnight
  3. concentrationThe reaction mixture was concentrated
  4. dissolutionresidue was dissolved in 200 ml of ethyl acetate
  5. custompartitioned with water
  6. washThe organic layer was washed with brine
  7. dry with materialOrganic layer was dried over anhydrous sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. washeluted with hexane:ethyl acetate (8:2)

Sources & evidence

ORD record
ord-96724c11222e4d60b344b7aa91a18f82
Source dataset
uspto-grants-2014_05
Patent number
US08722930B2

Reaction notes

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