p-Toluenesulfonic acid → 8Fluoro-1-hydroxy-5-methoxy-naphthalene

HRID 374658Notes

Reaction equation

HRID 374658 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]2[C:11]=1[C:10](=[O:12])[CH2:9][CH2:8][CH2:7]2.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>C(OC(C)=C)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]2[C:11]=1[C:10]([OH:12])=[CH:9][CH:8]=[CH:7]2

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 108563538-Fluoro-3,4-dihydro-5-methoxy-1(2H)-naphthalenone

Product 1

HCID 189969698Fluoro-1-hydroxy-5-methoxy-naphthalene

Reagents, catalysts & solvents 1

HCID 7916Isopropenyl acetateSolvent

Procedure

8-Fluoro-5-methoxy-l-tetralone (20 g) was dissolved in isopropenyl acetate (70 ml), p-toluenesulphonic acid (1 g) was added and the mixture was heated under reflux under nitrogen for 5 days. The reaction mixture was poured into aqueous sodium hydrogen carbonate solution (250 ml) and the crude product extracted into ethyl acetate (3×100 ml). The combined organic extracts were dried over magnesium sulphate, filtered and the solvent removed under reduced pressure. The resulting dark oil was taken up into dioxan (200 ml) and dichlorodicyanobenzoquinone (DDQ) (25 g) was added. The solution was heated under reflux for 18 hours and filtered to remove DDQ residues. The solvent was removed under reduced pressure and the crude product purified by chromatography on silica (eluent hexane/ethyl acetate 3:1). The resulting red oil was dissolved in methanol (100 ml) and heated under reflux with sodium hydroxide (9 g) for 1 hour. Water (100 ml) was added and the mixture was washed with ether/hexane 1:1 (200 ml). The aqueous phase was acidified and the product collected by filtration to give a dark solid after drying.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under nitrogen for 5 days
  3. extractionthe crude product extracted into ethyl acetate (3×100 ml)
  4. dry with materialThe combined organic extracts were dried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. additionwas added
  8. temperatureThe solution was heated
  9. temperatureunder reflux for 18 hours
  10. filtrationfiltered
  11. customto remove DDQ residues
  12. customThe solvent was removed under reduced pressure
  13. customthe crude product purified by chromatography on silica (eluent hexane/ethyl acetate 3:1)
  14. dissolutionThe resulting red oil was dissolved in methanol (100 ml)
  15. temperatureheated
  16. temperatureunder reflux with sodium hydroxide (9 g) for 1 hour
  17. additionWater (100 ml) was added
  18. washthe mixture was washed with ether/hexane 1:1 (200 ml)
  19. filtrationthe product collected by filtration
  20. customto give a dark solid
  21. customafter drying

Sources & evidence

ORD record
ord-f696a5a4b7ac4e89b540ccb705e4a165
Source dataset
uspto-grants-1996_01
Patent number
US05480873

Reaction notes

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