4-Bromoanisole → 7-Methoxy-4-(4-methoxyphenyl)-1,2-dihydronaphthalene

HRID 1651227Notes

Reaction equation

HRID 1651227 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.BrC1C=CC(OC)=CC=1.[Mg].[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29](=O)[CH2:28][CH2:27][CH2:26]2>O1CCCC1.C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[C:6](=[CH:5][CH:4]=1)[C:29]([C:30]1[CH:31]=[CH:32][C:23]([O:22][CH3:21])=[CH:24][CH:25]=1)=[CH:28][CH2:27][CH2:26]2

Participants

9

Reactant 4

HCID 77304-BromoanisoleHCID 141126-Methoxy-alpha-tetraloneHCID 5462224MagnesiumHCID 178491912HCID 178491912, compound

Product 1

HCID 128714357-Methoxy-4-(4-methoxyphenyl)-1,2-dihydronaphthalene

Reagents, catalysts & solvents 4

HCID 6101p-Toluenesulfonic acidCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-methoxyphenyl magnesium bromide, freshly prepared in the normal manner in tetrahydrofuran (200 mL) from 4-bromoanisole (101 g) and magnesium metal (14.5 g), was added over 45 minutes with stirring to a chilled (0° C.) solution of 6-methoxytetralone (85 g) in dry tetrahydrofuran (500 mL). After the addition was completed, the reaction was stirred at room temperature for 2 hours and the excess reagent was destroyed by the careful addition of water (50 mL). Most of the solvent was removed in vacuo and the concentrate was partitioned between ethyl acetate and 1N sodium hydroxide. After the resultant solids were filtered off, the layers were separated and the organic layer was washed with brine, then was dried (MgSO4) and evaporated to give 123 g of crude carbinol as an oil. A solution of the above carbinol (100 g) in toluene (800 mL) containing p-toluenesulfonic acid (1 g) was refluxed for 3 hours in a flask equipped with a Dean-Stark trap. The cooled solution was washed with 10% sodium bicarbonate solution and with brine, then was dried (MgSO4) and evaporated. The residual material was passed though a short column of silica gel (250 g) made up in dichloromethane-hexane (1:3) and the product was eluted with dichloromethane-hexane (1:1). Evaporation of the appropriate fractions and crystallization of the residue from toluene-hexane (2x) gave 37.1 g of 3,4-dihydro-6-methoxy-1-(4-methoxyphenyl)naphthalene, mp 100.5°-102° C.

Workup

  1. additionwas added over 45 minutes
  2. additionAfter the addition
  3. stirringthe reaction was stirred at room temperature for 2 hours
  4. customthe excess reagent was destroyed by the careful addition of water (50 mL)
  5. customMost of the solvent was removed in vacuo
  6. customthe concentrate was partitioned between ethyl acetate and 1N sodium hydroxide
  7. filtrationAfter the resultant solids were filtered off
  8. customthe layers were separated
  9. washthe organic layer was washed with brine
  10. dry with materialwas dried (MgSO4)
  11. customevaporated
  12. customto give 123 g of crude carbinol as an oil
  13. temperaturewas refluxed for 3 hours in a flask
  14. customequipped with a Dean-Stark trap
  15. washThe cooled solution was washed with 10% sodium bicarbonate solution and with brine
  16. dry with materialwas dried (MgSO4)
  17. customevaporated
  18. washthe product was eluted with dichloromethane-hexane (1:1)
  19. customEvaporation of the appropriate fractions and crystallization of the residue from toluene-hexane (2x)

Sources & evidence

ORD record
ord-08a20f61c487411a86e533743fabebae
Source dataset
uspto-grants-1990_05
Patent number
US04927838

Reaction notes

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