Pyridine → N-[4-chloro-2-hydroxy-5-trifluoromethylphenyl]isonicotinamide

HRID 2190841Notes

Reaction equation

HRID 2190841 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([Cl:12])=[CH:4][C:3]=1[OH:13].CCN=C=NCCCN(C)C.[C:25](O)(=[O:32])[C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1.N1C=CC=CC=1>O>[Cl:12][C:5]1[C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]([NH:1][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=2)=[C:3]([OH:13])[CH:4]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 5922Isonicotinic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 140117362-Amino-5-chloro-4-(trifluoromethyl)phenol

Product 1

HCID 66880038N-[4-chloro-2-hydroxy-5-trifluoromethylphenyl]isonicotinamideYield 58.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1.2 g of 2-amino-5-chloro-4-trifluoromethylphenol, 1.35 g of WSC, 0.67 g of isonicotinic acid and 10 ml of pyridine was stirred while heating at 80° C. for three hours. The reaction mixture was cooled to room temperature, and then water was added, followed by extraction with ethyl acetate three times. The combined organic layers were washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 1.01 g of N-[4-chloro-2-hydroxy-5-trifluoromethylphenyl]isonicotinamide.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate three times
  3. washThe combined organic layers were washed with water
  4. dry with materiala saturated sodium chloride solution, dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1c13a679d4384b51b013acb614b0182a
Source dataset
uspto-grants-2012_12
Patent number
US08324387B2

Reaction notes

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