Hydrochloric Acid → 3-t-Butyl-5-hydroxybenzoic acid

HRID 658014Notes

Reaction equation

HRID 658014 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)[C:5]([OH:7])=[O:6].C([Li])CCC.B(OC)(OC)[O:21]C.[OH-].[Na+].OO.Cl>C1COCC1.O.CC(=O)OCC>[C:11]([C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([OH:21])[CH:10]=1)[C:5]([OH:7])=[O:6])([CH3:14])([CH3:13])[CH3:12]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 8470Trimethyl borateHCID 14798Sodium HydroxideHCID 210882993-Bromo-5-tert-butylbenzoic acidHCID 178418339Butyllithium

Product 1

HCID 217986673-t-Butyl-5-hydroxybenzoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Bromo-5-tert-butylbenzoic acid (5 g) was dissolved in THF (180 ml), and n-butyllithium (18.7 ml, 2.5 M in hexane) was added dropwise under argon and at −75° C., and stirred for a further 30 min. Then trimethyl borate (6.63 ml) was added dropwise and the mixture was allowed to come to RT within 1 h. Thereafter, sodium hydroxide (0.778 g), dissolved in 2 ml of water, and hydrogen peroxide (12.89 ml, 30%) were added in succession. After stirring at RT for 3 h, the mixture was left to stand over the weekend. Then water and EA were added, the mixture was adjusted to pH 3 with 1 N hydrochloric acid and the EA phase was removed. This phase was washed three times with water, dried, filtered and concentrated. The residue was purified using silica gel (120 g cartridge, n-heptane/MtB ether gradient of 0-50% in 60 min). 1.94 g of the title compound were obtained.

Workup

  1. waitto come to RT within 1 h
  2. stirringAfter stirring at RT for 3 h
  3. waitthe mixture was left
  4. customthe EA phase was removed
  5. washThis phase was washed three times with water
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified
  10. customsilica gel (120 g cartridge, n-heptane/MtB ether gradient of 0-50% in 60 min)

Sources & evidence

ORD record
ord-54163e459cff4066a8b9b3de71f9dc10
Source dataset
uspto-grants-2011_12
Patent number
US08076336B2

Reaction notes

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