Hydrochloric Acid → 3-Ethyl-4-benzyloxy-5-methylphenol

HRID 323686Notes

Reaction equation

HRID 323686 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:4]([CH2:17][CH3:18])[CH:3]=1.C([Li])CCC.C[O:25]B(OC)OC.Cl.OO>O1CCCC1.C1(C)C=CC=CC=1>[CH2:17]([C:4]1[CH:3]=[C:2]([OH:25])[CH:7]=[C:6]([CH3:8])[C:5]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:18]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 8470Trimethyl borateHCID 220068134-Bromo-2-ethyl-6-methyl-1-benzyloxybenzeneHCID 178418339Butyllithium

Product 1

HCID 220067253-Ethyl-4-benzyloxy-5-methylphenolYield 93%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Then, 35.6 g of 4-bromo-2-ethyl-6-methyl-1-benzyloxybenzene was dissolved in 250 ml of tetrahydrofuran, and 69 ml of n-butyl lithium solution (in hexane; 1.69 mol/liter), while stirring at-70° C. After further stirring at 70° C. for 2 hours, a solution of 12.1 g of trimethoxyboron dissolved in 50 ml of tetrahydrofuran was added dropwise to the reaction mixture. After completion of the dropwise addition, the reaction mixture was returned to room temperature, stirred for 1 hour, and then poured into ice water. The mixture was made weak acidic by the addition of 10% hydrochloric acid, and extracted twice with 500 ml of diethyl ether. The ether layers was combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a residue. To the residue was added 120 ml of toluene, and 33 ml of 30% aqueous hydrogen peroxide was added dropwise, while heating at 70° C. under stirring. After heating under reflux for 1 hours, the reaction mixture was returned to room temperature, washed once with water, twice with 10% aqueous ferrous ammonium sulfate and then once with water. The toluene layer was dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 26.2 g of 3-ethyl-4-benzyloxy-5-methylphenol (93% yield).

Workup

  1. additionwas added dropwise to the reaction mixture
  2. additionAfter completion of the dropwise addition
  3. customwas returned to room temperature
  4. stirringstirred for 1 hour
  5. extractionextracted twice with 500 ml of diethyl ether
  6. washwashed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customto give a residue
  10. additionwas added dropwise
  11. temperaturewhile heating at 70° C.
  12. stirringunder stirring
  13. temperatureAfter heating
  14. temperatureunder reflux for 1 hours
  15. customwas returned to room temperature
  16. washwashed once with water, twice with 10% aqueous ferrous ammonium sulfate
  17. dry with materialThe toluene layer was dried over anhydrous magnesium sulfate
  18. concentrationconcentrated
  19. customto give a crude product

Sources & evidence

ORD record
ord-8fe2cecd06434011b12724581b79a6af
Source dataset
uspto-grants-2001_04
Patent number
US06214835B1

Reaction notes

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