Potassium Carbonate → 5-Chloro-2-[(5-chloropyridin-3-yl)oxy]nicotinic acid

HRID 1293185Notes

Reaction equation

HRID 1293185 reaction equation
Cl[C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([OH:19])[CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.[Cu]>[Cl:11][C:8]1[CH:9]=[N:10][C:2]([O:19][C:17]2[CH:16]=[N:15][CH:14]=[C:13]([Cl:12])[CH:18]=2)=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 5823053-Hydroxy-5-chloropyridineHCID 27360852,5-Dichloropyridine-3-carboxylic acid

Product 1

HCID 575722875-Chloro-2-[(5-chloropyridin-3-yl)oxy]nicotinic acidYield 47.1%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2,5-dichloronicotinic acid (Syn. Commun. 1989, 19, 553–9, 500 mg, 2.6 mmol), 3-chloro-5-hydroxypyridine (404 mg, 3.1 mmol), copper bronze (36 mg, 0.57 mmol), cuprous iodide (40 mg, 0.21 mmol) and potassium carbonate (792 mg, 5.7 mmol) in N,N-dimethylforamide (7 mL) was heated under reflux for 3 h. The reaction mixture was filtered through a pad of Celite® and the filtrate was concentrated. The residue was diluted with water (10 mL) and the mixture was acidified with 2 N hydrochloric acid (2 mL). Precipitateed solids were collected by filtration and dried under reduced presssure at 40° C. to afford 349 mg of the title compound: 1H-NMR (CDCl3) δ 8.37 (3H, br.s), 7.96 (2H, br.s), a peak of COOH was not observed; MS (ESI) m/z 285 (M+H)+.—

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 h
  3. filtrationThe reaction mixture was filtered through a pad of Celite®
  4. concentrationthe filtrate was concentrated
  5. additionThe residue was diluted with water (10 mL)
  6. filtrationPrecipitateed solids were collected by filtration
  7. customdried
  8. customat 40° C.

Sources & evidence

ORD record
ord-fbf86aeab38744bebef73263e2fb9860
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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