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

HRID 232251Notes

Reaction equation

HRID 232251 reaction equation
[OH-:1].[Na+].O.CC[C@@H]1[C@@H]2C[C@@H]([C@H](O)C3C=CN=[C:21]4[C:16]=3[CH:17]=[C:18]([O:25][CH3:26])[CH:19]=[CH:20]4)N(CC2)C1.[Cl:28][C:29]1[CH:30]=[C:31]([F:36])C(F)=[N:33][CH:34]=1>CS(C)=O>[Cl:28][C:29]1[CH:30]=[C:31]([F:36])[C:26]([O:25][C:18]2[CH:17]=[CH:16][C:21]([OH:1])=[CH:20][CH:19]=2)=[N:33][CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 121515(-)-DihydroquinineHCID 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 hydroquinine (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. additionAqueous NaOh was added to pH 12
  4. filtrationthe solid diether side-product was filtered off
  5. extractionextracted with ether
  6. additiontreated with Norite adsorbent
  7. customthe solvent was removed by rotary evaporation
  8. customto give a yellow oil which
  9. customwas purified by high pressure liquid chromatography (HPLC) (80% hexane/20% ethyl acetate)

Sources & evidence

ORD record
ord-618047ac7c4c484784571b233cd1e6c2
Source dataset
uspto-grants-1989_07
Patent number
US04851539

Reaction notes

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