Trimethyl borate → 3-tert-butyl-5-bromophenol

HRID 2071040Notes

Reaction equation

HRID 2071040 reaction equation
[Li]CCCC.[Br:6][C:7]1[CH:12]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:10]=[C:9](Br)[CH:8]=1.B(OC)(OC)[O:19]C>C1COCC1>[Br:6][C:7]1[CH:8]=[C:9]([OH:19])[CH:10]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:12]=1

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 27611701,3-dibromo-5-tert-butylbenzeneHCID 178418339Butyllithium

Product 1

HCID 578373843-tert-butyl-5-bromophenol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 34 mL of 1.6 M n-BuLi in hexanes in 20 mL of THF at −78° C. was added 8.15 g of 1,3-dibromo-5-tert-butylbenzene in 80 mL of THF dropwise over a period of 1 h. After 1 h at −78° C., 4.6 mL of B(OMe)3 was added, and after 20 min. the cold bath was removed and stirring continued with warming to r.t. After 1 h, EtOAc and 70 mL of 1 N HCl were added, and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. To a stirring mixture of the crude product in 105 mL of 1 N NaOH at 0° C. was added 22 mL of H2O2 (30 wt % in H2O) dropwise. After 25 min. 5 N HCl was added to a pH=1. Ethyl acetate was added, and the organic layer was washed with 80 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (hexanes to 10% EtOAc/hexanes) provided 6.54 g of 3-bromo-5-tert-butylphenol as an orange oil with some impurity.

Workup

  1. customafter 20 min. the cold bath was removed
  2. waitAfter 1 h
  3. additionEtOAc and 70 mL of 1 N HCl were added
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionTo a stirring mixture of the crude product in 105 mL of 1 N NaOH at 0° C.
  10. additionwas added 22 mL of H2O2 (30 wt % in H2O) dropwise
  11. waitAfter 25 min
  12. addition5 N HCl was added to a pH=1
  13. additionEthyl acetate was added
  14. washthe organic layer was washed with 80 mL of brine
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customPurification by flash silica gel chromatography (hexanes to 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d3e4bf4377f94c129b1be5f1c232bb8f
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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