Triethylamine → 3-chloro-N-[2-hydroxy-5-(trifluoromethoxy)phenyl]isonicotinamide

HRID 1913741Notes

Reaction equation

HRID 1913741 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[OH:13].[Cl:14][C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17](O)=[O:18].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>O.CN(C=O)C>[Cl:14][C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17]([NH:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:10])([F:11])[F:12])[CH:5]=[CH:4][C:3]=1[OH:13])=[O:18]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate2×HCID 27358163-Chloropyridine-4-carboxylic acidHCID 27377292-Amino-4-(trifluoromethoxy)phenol

Product 1

HCID 668800333-chloro-N-[2-hydroxy-5-(trifluoromethoxy)phenyl]isonicotinamideYield 71.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.35 g of 2-amino-4-trifluoromethoxy phenol, 0.29 g of 3-chloroisonicotinic acid, 1.04 g of (benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (hereinafter, referred to as a BOP reagent), 0.24 g of triethylamine and 5 ml of DMF was stirred at room temperature for two hours. Water was added to the reaction mixture, precipitated solid was collected by filtration. The resultant solid was dissolved in ethyl acetate. Then, the organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.43 g of 3-chloro-N-[2-hydroxy-5-(trifluoromethoxy)phenyl]isonicotinamide.

Workup

  1. customprecipitated solid
  2. filtrationwas collected by filtration
  3. dissolutionThe resultant solid was dissolved in ethyl acetate
  4. washThen, the organic layer was washed with a saturated sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5184e5ef3e4d4acba047f110b3e79783
Source dataset
uspto-grants-2013_12
Patent number
US08609705B2

Reaction notes

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