Water → 4-(4-tert-butylphenyl)-2-methylindan-2-ol

HRID 1269482Notes

Reaction equation

HRID 1269482 reaction equation
C([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:7]([CH2:17]Cl)[C:6]=1[CH2:19]Cl)(C)(C)C.[C:21]([O:24]C)(=O)[CH3:22].O>BrCCBr.C1COCC1>[C:6]([C:14]1[CH:15]=[CH:16][C:11]([C:8]2[CH:9]=[CH:10][CH:5]=[C:6]3[C:7]=2[CH2:17][C:21]([CH3:22])([OH:24])[CH2:19]3)=[CH:12][CH:13]=1)([CH3:19])([CH3:7])[CH3:5]

Participants

6

Reactant 3

HCID 962WaterHCID 6584Methyl AcetateHCID 18448812HCID 18448812, compound

Product 1

HCID 116305434-(4-tert-butylphenyl)-2-methylindan-2-ol

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

633 mg (26 mmol, 4 eq.) of Mg powder (50 mesh/Aldrich) were dried under reduced pressure with the aid of a hair dryer. 10 ml of THF and 10 drops of 1,2-dibromoethane were added. The mixture was heated to reflux until gas evolution took place and the activation was complete. The solvent was removed under reduced pressure and 10 ml of fresh THF were added. A solution of 2.0 g (6.5 mmol) of tert-butyl-2,3-bis(chloromethyl)biphenyl in 120 ml of THF was added and the suspension was stirred vigorously at room temperature for 3 hours. Stirring was continued overnight and the slightly greenish turbid solution obtained was filtered to remove excess magnesium. The filtrate was cooled to −78° C. and a solution of 482 mg (6.51 mol) of methyl acetate in 60 ml of THF was added dropwise over a period of 1 hour. The reaction solution was warmed to 0° C. over a period of 2 hours. 80 ml of water were subsequently added and the solution was concentrated under reduced pressure. To dissolve the magnesium salts, 3 ml of concentrated hydrochloric acid were added and the aqueous phase was extracted with methylene chloride (3×50 ml). The combined organic phases were dried over magnesium sulfate, and the solvent was subsequently removed under reduced pressure. The product was purified by column chromatography, with the nonpolar by-products being separated off using a heptane/dichloromethane mixture and the product being eluted with pure dichloromethane, giving a yellow product. Yield: 0.64 g (2.28 mmol/35%/94.5% by GC). 1H NMR (400 MHz, CDCl3): δ=7.43–7.22 (m, 7H, aromat.), 3.08 (m, 4H, CH2), 1.48 (s, 3H, CH3), 1.35 (s, 9H, tert-butyl) ppm.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux until gas evolution
  3. customThe solvent was removed under reduced pressure and 10 ml of fresh THF
  4. additionwere added
  5. stirringStirring
  6. waitwas continued overnight
  7. customthe slightly greenish turbid solution obtained
  8. filtrationwas filtered
  9. customto remove excess magnesium
  10. temperatureThe filtrate was cooled to −78° C.
  11. temperatureThe reaction solution was warmed to 0° C. over a period of 2 hours
  12. concentrationthe solution was concentrated under reduced pressure
  13. dissolutionTo dissolve the magnesium salts, 3 ml of concentrated hydrochloric acid
  14. additionwere added
  15. extractionthe aqueous phase was extracted with methylene chloride (3×50 ml)
  16. dry with materialThe combined organic phases were dried over magnesium sulfate
  17. customthe solvent was subsequently removed under reduced pressure
  18. customThe product was purified by column chromatography, with the nonpolar by-products
  19. custombeing separated off
  20. washthe product being eluted with pure dichloromethane
  21. customgiving a yellow product

Sources & evidence

ORD record
ord-f73b45d6ac9041bda94428640af425ea
Source dataset
uspto-grants-2007_04
Patent number
US07199274B2

Reaction notes

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