Cesium carbonate → 2-(1,3-Benzodioxol-5-yloxy)pyridine-3-carboxylic acid

HRID 350972Notes

Reaction equation

HRID 350972 reaction equation
C([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][C:6]=1Cl)C.[O:13]1[C:17]2[CH:18]=[CH:19][C:20]([OH:22])=[CH:21][C:16]=2[O:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[OH-].[Li+].O>[O:13]1[C:17]2[CH:18]=[CH:19][C:20]([O:22][C:6]3[N:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:4]([OH:3])=[O:12])=[CH:21][C:16]=2[O:15][CH2:14]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 68289SesamolHCID 2796614Ethyl chloronicotinate

Product 1

HCID 27368792-(1,3-Benzodioxol-5-yloxy)pyridine-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3939Lithium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Chloro-nicotinic acid ethyl ester (10 g), benzo[1,3]dioxol-5-ol (sesamol, 8.2 g), and cesium carbonate (21 g) were mixed in anhydrous dioxane (40 mL) and the resulting slurry heated to reflux for 16 h. In a separate flask, lithium hydroxide (12.9 g) was dissolved in water (80 mL) with warming and then added to the refluxing mixture, which was heated for an additional 4 h. The mixture was cooled to ambient temperature and concentrated in vacuo to remove the dioxane. Concentrated hydrochloric acid was added dropwise until the pH=3. The acidified solution was then extracted with ethyl acetate (7×100 mL) to yield crude product, which was recrystallized from ethyl acetate to yield the purified title compound (10.8 g).

Workup

  1. temperaturethe resulting slurry heated
  2. temperatureto reflux for 16 h
  3. temperaturewith warming
  4. additionadded to the refluxing mixture, which
  5. temperaturewas heated for an additional 4 h
  6. concentrationconcentrated in vacuo
  7. customto remove the dioxane
  8. additionConcentrated hydrochloric acid was added dropwise until the pH=3
  9. extractionThe acidified solution was then extracted with ethyl acetate (7×100 mL)
  10. customto yield crude product, which
  11. customwas recrystallized from ethyl acetate
  12. customto yield the
  13. custompurified title compound (10.8 g)

Sources & evidence

ORD record
ord-d393aad1e2d34ab7a46739b8c9a67895
Source dataset
uspto-grants-2007_02
Patent number
US07183293B2

Reaction notes

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