3-Hydroxypyridine → HCID 178505469, compound

HRID 508583Notes

Reaction equation

HRID 508583 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]2[NH:6][C:7]([CH:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=3)[OH:10])=[N:8][C:4]=2[CH:3]=1.S(Cl)(Cl)=O.O[C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1.[OH-].[K+].[OH-].[Na+]>C1COCC1.N1C=CC=CC=1>[F:1][C:2]1[CH:23]=[CH:22][C:5]2[NH:6][C:7]([CH:9]([O:10][C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]([F:20])([F:19])[F:21])=[CH:13][CH:12]=3)=[N:8][C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 79713-HydroxypyridineHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 178519719HCID 178519719, compound

Product 1

HCID 178505469HCID 178505469, compoundYield 10.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

The compound of Example 1 (150 mg) was dissolved in THF (5 mL), and thionyl chloride (60 mg) and pyridine (146 mg) were added thereto. The mixture was stirred for 30 minutes at room temperature, and then 3-hydroxypyridine (87 mg) and potassium hydroxide (65 mg) were added thereto. The mixture was heated to reflux for 30 minutes while being stirred. A 10% aqueous solution of sodium hydroxide was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (60% to 100% ethyl acetate/hexane), and thus the title compound (19 mg) was obtained as a yellow amorphous material.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 30 minutes
  3. stirringwhile being stirred
  4. extractionthe mixture was extracted with chloroform
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationAfter distilling off the solvent under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (60% to 100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e5e7932b8e6b44d1a8cbd50696bbfaa1
Source dataset
uspto-grants-2015_08
Patent number
US09096531B2

Reaction notes

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