Sodium Carbonate → 6-(4-(Methylsulfonyl)phenyl)pyridin-3-ol

HRID 423685Notes

Reaction equation

HRID 423685 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][S:10]([C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1)(=[O:12])=[O:11].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([C:2]2[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=2)=[CH:15][CH:14]=1)(=[O:12])=[O:11]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 27628652-Bromo-5-hydroxypyridine

Product 1

HCID 532295926-(4-(Methylsulfonyl)phenyl)pyridin-3-olYield 20%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 6-bromo-3-pyridinol (1.28 g, 7.35 mmol), [4-(methylsulfonyl)phenyl]boronic acid (1.47 g, 7.35 mmol), and 2M Na2CO3 (5 mL) in DMF (15 mL) was treated with PdCl2(PPh3)2 (0.52 g, 0.74 mmol) and the mixture was heated at 50° C. overnight. The reaction was treated with additional catalyst (PdCl2(PPh3)2, 0.26 g, 0.37 mmol) and was heated at 50° C. overnight, then was heated at 90° C. overnight. The reaction was allowed to cool to room temperature and was diluted with EtOAc and water and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated. The resulting residue was treated with MeOH and cooled in an ice bath. The resulting precipitate was collected, washed with cold MeOH and air-dried and the filtrates were combined and set aside. The resulting tan solid was dissolved in 10% MeOH/CH2Cl2 and loaded onto a 220 g silica column, which was eluted with 1 to 5% MeOH/CH2Cl2 over 30 min, followed by 5% MeOH/CH2Cl2 for 30 min to provide 6-[4-(methylsulfonyl)phenyl]-3-pyridinol (0.36 g, 20%) as a tan solid. The mother liquors from the MeOH trituration step were concentrated and purified by chromatography 1 to 5% MeOH/CH2Cl2 over 20 min to provide additional product (0.24 g, 33% overall yield) as a tan solid.

Workup

  1. temperaturewas heated at 50° C. overnight
  2. temperaturewas heated at 90° C. overnight
  3. temperatureto cool to room temperature
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionThe resulting residue was treated with MeOH
  9. temperaturecooled in an ice bath
  10. customThe resulting precipitate was collected
  11. washwashed with cold MeOH
  12. customair-dried
  13. dissolutionThe resulting tan solid was dissolved in 10% MeOH/CH2Cl2
  14. washwas eluted with 1 to 5% MeOH/CH2Cl2 over 30 min

Sources & evidence

ORD record
ord-d7bf0e443b36437899340e7a1a6505a4
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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