Dimethylformamide → N-[4-chloro-2-hydroxy-5-(trifluoromethyl)phenyl]-3-ethyl isonicotinamide

HRID 1913733Notes

Reaction equation

HRID 1913733 reaction equation
[CH2:1]([C:3]1[CH:11]=[N:10][CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6])[CH3:2].CN(C=O)C.[NH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[C:21]([Cl:28])=[CH:20][C:19]=1[OH:29].C(N(CC)CC)C>O>[Cl:28][C:21]1[C:22]([C:24]([F:27])([F:26])[F:25])=[CH:23][C:18]([NH:17][C:5](=[O:6])[C:4]2[CH:8]=[CH:9][N:10]=[CH:11][C:3]=2[CH2:1][CH3:2])=[C:19]([OH:29])[CH:20]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 140117362-Amino-5-chloro-4-(trifluoromethyl)phenolHCID 871891373-Ethyl isonicotinic acid chloride

Product 1

HCID 66880000N-[4-chloro-2-hydroxy-5-(trifluoromethyl)phenyl]-3-ethyl isonicotinamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 0.62 g of 3-ethyl isonicotinic acid 4 ml of thionyl chloride was heated to reflux for 2.5 hours. The reaction mixture was cooled to room temperature, the reaction mixture was concentrated under reduced pressure to give 3-ethyl isonicotinic acid chloride. A mixture of the resultant 3-ethyl isonicotinic acid chloride and 3 ml of DMF was added dropwise to a mixture of 0.87 g of 2-amino-5-chloro-4-trifluoromethylphenol, 0.83 g of triethylamine and 3 ml of DMF while ice-cooling. The reaction mixture was stirred at room temperature for two hours, 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 then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.23 g of N-[4-chloro-2-hydroxy-5-(trifluoromethyl)phenyl]-3-ethyl isonicotinamide.

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with ethyl acetate twice
  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-c28a401ae560442ca1961724d4697e77
Source dataset
uspto-grants-2013_12
Patent number
US08609705B2

Reaction notes

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