Sodium Hydroxide → 6-[2-Fluoro-4-(methylsulfonyl)phenyl]-3-pyridinol

HRID 423532Notes

Reaction equation

HRID 423532 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[C:4]([F:15])[CH:3]=1.[Na+].[CH3:17][S:18]([O-:20])=[O:19].[OH-].[Na+]>CS(C)=O>[F:15][C:4]1[CH:3]=[C:2]([S:18]([CH3:17])(=[O:20])=[O:19])[CH:7]=[CH:6][C:5]=1[C:8]1[N:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 2733271Sodium methanesulfinateHCID 666732076-(4-Bromo-2-fluorophenyl)-3-pyridinol

Product 1

HCID 666730256-[2-Fluoro-4-(methylsulfonyl)phenyl]-3-pyridinolYield 68.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-(4-bromo-2-fluorophenyl)-3-pyridinol (0.245 g, 0.91 mmol), methanesulfinic acid sodium salt (0.47 g, 80%, 3.66 mmol), Cul (0.70 g, 3.66 mmol) and NaOH (44 mg, 1.10 mmol) in DMSO (20 mL) was degassed with N2 three times and heated at 120° C. overnight. After the mixture was cooled to ambient temperature, 1N HCl was added to adjust the aqueous pH to about 8. The mixture was extracted with EtOAc. The combined organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a light brown viscous oil. The crude product was purified by chromatography on a silica gel column eluted with 2:4:0.1 EtOAc/CH2Cl2/MeOH to give 0.166 g (68%) of 6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinol as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.26 (d, 1H, J=2.7 Hz), 8.15-8.05 (m, 1H), 7.90-7.75 (m, 2H), 7.74 (dd, 1H, Ja=8.6 Hz, Jb=2.1 Hz), 7.32 (dd, 1H, Ja=8.6 Hz, Jb=2.8 Hz), 3.18 (s, 3H); LRMS (ESI), m/z 268 (M+H).

Workup

  1. customwas degassed with N2 three times
  2. temperatureAfter the mixture was cooled to ambient temperature
  3. addition1N HCl was added
  4. extractionThe mixture was extracted with EtOAc
  5. extractionThe combined organic extract
  6. washwas washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customto give the crude product as a light brown viscous oil
  11. customThe crude product was purified by chromatography on a silica gel column
  12. washeluted with 2:4:0.1 EtOAc/CH2Cl2/MeOH

Sources & evidence

ORD record
ord-706382dcd4e54699973aeaa778417975
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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