Dimethyl Sulfoxide → 7,8-difluoroquinolin-3-ol

HRID 1618913Notes

Reaction equation

HRID 1618913 reaction equation
[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[C:7](I)[CH:8]=[N:9]2)=[CH:4][CH:3]=1.CS(C)=[O:16].[OH-].[Na+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>[Cu]I.O>[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[C:7]([OH:16])[CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 13181,10-PhenanthrolineHCID 14798Sodium HydroxideHCID 68285982HCID 68285982, compound

Product 1

HCID 682855737,8-difluoroquinolin-3-olYield 95%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

In a 3 L eggplant-shaped flask containing a stir bar, 7,8-difluoro-3-iodoquinoline (227.2 g, 0.78 mol), dimethylsulfoxide (600 mL), and water (600 mL) were introduced and sodium hydroxide (131.5 g, 2.34 mol), CuI (14.8 g, 0.078 mol), and 1,10-phenanthroline (28.1 g, 0.156 mol) were added. The mixture was further heated to 100° C. in an oil bath and was stirred for 24 hours. After cooling, the organic layer was removed by adding ethyl acetate and water. The thus obtained aqueous layer was neutralized with concentrated hydrochloric acid, and then the precipitated crystals were filtered and dried. On the other hand, after the filtrate was extracted with ethyl acetate, dried with magnesium sulfate, filtered and concentrated, the crude product obtained was purified by silica gel column chromatography (normal hexane:ethyl acetate) to obtain 133.7 g (95%) of 7,8-difluoro-3-hydroxyquinoline as a hazel solid combined with the previously obtained crystals.

Workup

  1. additionIn a 3 L eggplant-shaped flask containing a stir bar
  2. temperatureAfter cooling
  3. customthe organic layer was removed
  4. additionby adding ethyl acetate and water
  5. filtrationthe precipitated crystals were filtered
  6. customdried
  7. extractionOn the other hand, after the filtrate was extracted with ethyl acetate
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customthe crude product obtained
  12. customwas purified by silica gel column chromatography (normal hexane:ethyl acetate)

Sources & evidence

ORD record
ord-8396c8f22c124b5d951e936de329bcd1
Source dataset
uspto-grants-2014_07
Patent number
US08772200B2

Reaction notes

Loading…