Hydroquinone → 4-((5-Chloro-3-fluoro-2-pyridinyl)oxy)phenol

HRID 1285092Notes

Reaction equation

HRID 1285092 reaction equation
[OH-].[Na+].O.[C:4]1([CH:11]=[CH:10][C:8]([OH:9])=[CH:7][CH:6]=1)[OH:5].[Cl:12][C:13]1[CH:14]=[C:15]([F:20])[C:16](F)=[N:17][CH:18]=1>CS(C)=O>[Cl:12][C:13]1[CH:14]=[C:15]([F:20])[C:16]([O:5][C:4]2[CH:11]=[CH:10][C:8]([OH:9])=[CH:7][CH:6]=2)=[N:17][CH:18]=1

Participants

6

Reactant 4

HCID 785HydroquinoneHCID 962WaterHCID 14798Sodium Hydroxide2×HCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 155928384-((5-Chloro-3-fluoro-2-pyridinyl)oxy)phenolYield 26.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of NaOH (1.76 g, 0.044 mol) in a few ml of water was added to hydroquinone (4.86 g, 0.040 mol) in 250 ml DMSO. The mixture was stirred under nitrogen for 20 minutes. 5-Chloro-2,3-difluoropyridine (6.0 g, 0.040 mol) was added. The reaction mixture was heated at 60°-70° C. for 3 hours, then poured over ice. Aqueous NaOH was added to pH 12 and the solid diether side-product was filtered off. The filtrate was acidified, extracted with ether, treated with Norite adsorbent, and the solvent was removed by rotary evaporation to give a yellow oil which solidified on standing and was purified by high pressure liquid chromatography (HPLC) (80% hexane/20% ethyl acetate) to give a white solid (2.5 g, 26% yield, m.p. 90°-92° C.).

Workup

  1. temperatureThe reaction mixture was heated at 60°-70° C. for 3 hours
  2. additionpoured over ice
  3. filtrationthe solid diether side-product was filtered off
  4. extractionextracted with ether
  5. additiontreated with Norite adsorbent
  6. customthe solvent was removed by rotary evaporation
  7. customto give a yellow oil which
  8. customwas purified by high pressure liquid chromatography (HPLC) (80% hexane/20% ethyl acetate)

Sources & evidence

ORD record
ord-9dac8be70afa4ffe8883202e86373883
Source dataset
uspto-grants-1986_01
Patent number
US04565568

Reaction notes

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