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

HRID 1762396Notes

Reaction equation

HRID 1762396 reaction equation
[C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].[OH-].[K+].[Cl:11][C:12]1[CH:13]=[C:14]([F:19])[C:15](F)=[N:16][CH:17]=1.Cl>CS(C)=O>[Cl:11][C:12]1[CH:13]=[C:14]([F:19])[C:15]([O:2][C:1]2[CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=2)=[N:16][CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 785HydroquinoneHCID 14797Potassium HydroxideHCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 155928384-((5-Chloro-3-fluoro-2-pyridinyl)oxy)phenolYield 68.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A mixture of 27.5 g (0.25 mol) of hydroquinone, 11.2 g (0.2 mol) of potassium hydroxide in 600 ml of dimethylsulfoxide is stirred at room temperature under a nitrogen atmosphere until everything is dissolved. A solution of 30 g (0.2 mol) of 5-chloro-2,3-difluoropyridine in 200 ml of dimethylsulfoxide is added dropwise thereto. The reaction mixture is then heated to 70° and stirred at that temperature for 4 hours. Then it is poured into ice/water and the mixture is acidified with hydrochloric acid, extracted with ethyl acetate, dried over magnesium sulfate, filtered and evaporated to dryness. The residue is taken up in a hexane/ethyl acetate 2:1 solvent and passed over a silocagel column for purification. After concentrating the eluate, the residue crystallizes to yield 33 g of white crystals, melting at 97°-98°.

Workup

  1. dissolutionis dissolved
  2. temperatureThe reaction mixture is then heated to 70°
  3. stirringstirred at that temperature for 4 hours
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. custompassed over a silocagel column for purification
  9. concentrationAfter concentrating the eluate, the residue
  10. customcrystallizes

Sources & evidence

ORD record
ord-58723de98e2b49f9b6a240bc8ebdb621
Source dataset
uspto-grants-1989_05
Patent number
US04832736

Reaction notes

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