Dimethylformamide → N-[2-hydroxy-5-(trifluoromethyl)phenyl]-3-(trifluoromethyl)isonicotinamide

HRID 2190857Notes

Reaction equation

HRID 2190857 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[N:10][CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].CN(C=O)C.[NH2:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=1[OH:30].C(N(CC)CC)C>O>[OH:30][C:21]1[CH:22]=[CH:23][C:24]([C:26]([F:27])([F:28])[F:29])=[CH:25][C:20]=1[NH:19][C:5](=[O:6])[C:4]1[CH:8]=[CH:9][N:10]=[CH:11][C:3]=1[C:2]([F:13])([F:12])[F:1]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 1202462-Amino-4-(trifluoromethyl)phenolHCID 871890234-Pyridinecarbonyl chloride, 3-(trifluoromethyl)-

Product 1

HCID 86651072N-[2-hydroxy-5-(trifluoromethyl)phenyl]-3-(trifluoromethyl)isonicotinamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 0.72 g of 3-trifluoromethyl isonicotinic acid and 4 ml of thionyl chloride was heated to reflux for 1.5 hours. The reaction mixture was cooled to room temperature, and the reaction mixture was concentrated under reduced pressure to give 3-trifluoromethyl isonicotinic acid chloride. A mixture of the resultant 3-trifluoromethyl isonicotinic acid chloride and 4 ml of DMF was added dropwise to a mixture of 0.66 g of 2-amino-4-trifluoromethylphenol, 0.76 g of triethylamine, 4 ml of DMF while ice-cooling. The reaction mixture was stirred at room temperature for one hour and stirred while heating at 50° C. for 2.5 hours. The reaction mixture was cooled to room temperature, and then water was added to the reaction mixture, followed by extraction with ethyl acetate twice. The combined organic layers were washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was washed with diethyl ether to give 0.62 g of N-[2-hydroxy-5-(trifluoromethyl)phenyl]-3-(trifluoromethyl)isonicotinamide.

Workup

  1. temperaturecooling
  2. stirringstirred
  3. temperaturewhile heating at 50° C. for 2.5 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionfollowed by extraction with ethyl acetate twice
  6. washThe combined organic layers were washed with water
  7. dry with materiala saturated sodium chloride solution, dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washThe residue was washed with diethyl ether

Sources & evidence

ORD record
ord-bac188571f444d8580d69fd35daee3b3
Source dataset
uspto-grants-2012_12
Patent number
US08324387B2

Reaction notes

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