Potassium Carbonate → 6-(4-Cyanophenoxy)-2-(4-trifluoromethoxyphenoxy)nicotinic acid ethyl ester

HRID 1024696Notes

Reaction equation

HRID 1024696 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7]([O:9][C:10](=[O:27])[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)=[N:13][C:12]=1Cl)[CH3:8].[F:28][C:29]([F:39])([F:38])[O:30][C:31]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=1>CN(C=O)C>[CH2:7]([O:9][C:10](=[O:27])[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)=[N:13][C:12]=1[O:37][C:34]1[CH:35]=[CH:36][C:31]([O:30][C:29]([F:28])([F:38])[F:39])=[CH:32][CH:33]=1)[CH3:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 70015p-(Trifluoromethoxy)phenolHCID 86665953HCID 86665953, compound

Product 1

HCID 676057626-(4-Cyanophenoxy)-2-(4-trifluoromethoxyphenoxy)nicotinic acid ethyl esterYield 94.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (60 mg, 0.43 mmol) was added to a stirred and cooled (0° C.) solution of 2-chloro-6-(4-cyano phenoxy)nicotinic acid ethyl ester 0.13 g (0.43 mmol) in 10 ml DMF and stirred for 10 min at the same temperature. This was followed by the addition of 76.5 mg (0.43 mmol) of 4-trifluoromethoxy phenol, dissolved in 2 ml of DMF, over a period of 10 min. After the addition was completed, the contents were allowed to stir at RT. This was followed by heating for 3 h at 80° C. The reaction mixture was concentrated under reduced pressure, poured into ice-cold water and dissolved in 50 ml of ethyl acetate. Organic layer was then washed with brine solution followed by water and the crude product was purified by column chromatography using hexane:ethyl acetate (8:2) to afford 0.18 g of the required product. Percentage purity: LCMS−ve mode): 20.12%.

Workup

  1. stirringstirred for 10 min at the same temperature
  2. additionAfter the addition
  3. stirringto stir at RT
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionpoured into ice-cold water
  6. dissolutiondissolved in 50 ml of ethyl acetate
  7. washOrganic layer was then washed with brine solution
  8. customthe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-7a43184c2d8e43cc9265eef113be0a6c
Source dataset
uspto-grants-2014_05
Patent number
US08722930B2

Reaction notes

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