Water → 7-Ethyl-1-methoxymethoxynaphthalene

HRID 654668Notes

Reaction equation

HRID 654668 reaction equation
OC([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C:12]([OH:14])=[CH:11][CH:10]=[CH:9]2)C.F[C:16](F)(F)[C:17](O)=O.[C:22]([O:25][CH2:26]C)(=O)C.O>O1CCCC1.N1C=CC=CC=1>[CH2:16]([C:5]1[CH:4]=[C:13]2[C:8]([CH:9]=[CH:10][CH:11]=[C:12]2[O:14][CH2:26][O:25][CH3:22])=[CH:7][CH:6]=1)[CH3:17]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 10330105HCID 10330105, compound

Product 1

HCID 224018957-Ethyl-1-methoxymethoxynaphthalene

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

270 g of 8-(1-hydroxyethyl)-1-naphthol was dissolved in 500 ml of tetrahydrofuran and 170 ml of pyridine, followed by dropping 357 g of anhydrous trifluoroacetic acid under ice-cooling conditions in 45 minutes. The reaction solution was agitated under ice-cooling conditions for 0.5 hours, after which 2 liters of ethyl acetate was added. After washing with a saturated saline solution, 1N hydrochloric acid, a saturated saline solution and a sodium hydrogencarbonate saturated aqueous solution in this order, the reaction solution was dried with anhydrous magnesium sulfate. Insoluble matters were removed by filtration and 3.75 liters of tetrahydrofuran was added to the resultant filtrate. 3.75 g of 10% palladium-carbon (water content:50%) was further added, followed by violent agitation in an atmosphere of hydrogen at 1 atm., for 6 hours. After removal of the palladium-carbon by filtration, the filtrate was concentrated to half in volume. The resultant residue was added under agitation to a saturated sodium hydrogencarbonate aqueous solution, followed by extraction with ethyl acetate. The resultant organic phase was washed with a saturated saline solution. After drying with anhydrous magnesium sulfate, the solvent was distilled off and the resultant residue was dissolved in 1 liter of N,N-dimethylformamide. 69 g of 60% sodium hydride was gently added to the solution under ice-cooling conditions, followed by agitation for further 20 minutes. 160 g of chloromethyl methyl ether was dropped in the resultant reaction solution so that the inner temperature did not exceed 20 C. After further agitation at room temperature for 30 minutes, the reaction solution was poured into iced water and extracted with ethyl acetate. The organic phase was washed with a saturated saline solution and dried with anhydrous magnesium sulfate. The solvent was distilled off, followed by purification by silica gel column chromatography (hexane), thereby obtaining 259 g of the captioned compound as a light yellow oily substance.

Workup

  1. temperaturecooling conditions in 45 minutes
  2. temperaturecooling conditions for 0.5 hours
  3. washAfter washing with a saturated saline solution, 1N hydrochloric acid
  4. dry with materiala saturated saline solution and a sodium hydrogencarbonate saturated aqueous solution in this order, the reaction solution was dried with anhydrous magnesium sulfate
  5. customInsoluble matters were removed by filtration and 3.75 liters of tetrahydrofuran
  6. additionwas added to the resultant filtrate
  7. addition3.75 g of 10% palladium-carbon (water content:50%) was further added
  8. customAfter removal of the palladium-carbon
  9. filtrationby filtration
  10. concentrationthe filtrate was concentrated to half in volume
  11. additionThe resultant residue was added under agitation to a saturated sodium hydrogencarbonate aqueous solution
  12. extractionfollowed by extraction with ethyl acetate
  13. washThe resultant organic phase was washed with a saturated saline solution
  14. dry with materialAfter drying with anhydrous magnesium sulfate
  15. distillationthe solvent was distilled off
  16. dissolutionthe resultant residue was dissolved in 1 liter of N,N-dimethylformamide
  17. addition69 g of 60% sodium hydride was gently added to the solution under ice-
  18. temperaturecooling conditions
  19. waitfollowed by agitation for further 20 minutes
  20. addition160 g of chloromethyl methyl ether was dropped in the resultant
  21. customreaction solution so that the inner temperature
  22. waitAfter further agitation at room temperature for 30 minutes
  23. extractionextracted with ethyl acetate
  24. washThe organic phase was washed with a saturated saline solution
  25. dry with materialdried with anhydrous magnesium sulfate
  26. distillationThe solvent was distilled off
  27. customfollowed by purification by silica gel column chromatography (hexane)

Sources & evidence

ORD record
ord-195367ce70f44540943b3077d3627b3a
Source dataset
uspto-grants-1992_07
Patent number
US05134111

Reaction notes

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