3-Hydroxyanthranilic Acid → 3-Hydroxy-2-(isonicotinamido)benzoic acid

HRID 415197

Reaction equation

HRID 415197 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[C:3]=1[NH2:11].N1C=CC=CC=1.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1>C1(C)C=CC=CC=1>[OH:1][C:2]1[C:3]([NH:11][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6]

Participants

5

Reactant 3

HCID 863-Hydroxyanthranilic AcidHCID 1049PyridineHCID 417436Pyridine-4-carbonyl chloride

Product 1

HCID 666209463-Hydroxy-2-(isonicotinamido)benzoic acidYield 77.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Thionyl chloride (10 mL) was added to isonicotinic acid (370 mg, 3 mmol) and the mixture was stirred at reflux for 6 hr. Thionyl chloride was evaporated under reduced pressure and the residues was dried in vacuum to get isonicotinoyl chloride. 3-Hydroxyanthranilic acid (153 mg, 1.0 mmol) and pyridine (240 mg, 3.0 mmol) were added to toluene (10 mL) and the mixture was stirred at room temperature for 30 min. Then isonicotinoyl chloride (420 mg, 3.0 mmol) was added. The mixture was stirred at room temperature for 30 min and then at 80° C. for 2 hr. The resulting mixture was extracted with ethyl acetate (100 mL×4) and concentrated. The crude product was purified by column chromatography (silica gel, PE: ethyl acetate 20:1 to 5:1) to obtain 3-hydroxy-2-(isonicotinamido)benzoic acid as a solid (200 mg, yield 77%). LC-MS (ESI) m/z 259 [M+1]−.

Workup

  1. stirringThe mixture was stirred at room temperature for 30 min
  2. waitat 80° C. for 2 hr
  3. extractionThe resulting mixture was extracted with ethyl acetate (100 mL×4)
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (silica gel, PE: ethyl acetate 20:1 to 5:1)

Sources & evidence

ORD record
ord-d933b9fb84c84f92bc0a5396c90d9555
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Linked notes

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