Boron tribromide → 4-tert-Butyl-3-hydroxy-benzoic acid methyl ester

HRID 1158464Notes

Reaction equation

HRID 1158464 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:13])([CH3:12])[CH3:11])=[C:6]([O:14]C)[CH:5]=1.B(Br)(Br)Br>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:11])([CH3:12])[CH3:13])=[C:6]([OH:14])[CH:5]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 68616936Methyl 4-(1,1-dimethylethyl)-3-methoxybenzoate

Product 1

HCID 233453414-tert-Butyl-3-hydroxy-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of borontribromide (3.38 mL, 35.1 mmol) in CH2Cl2 (35 mL), cooled to −60° C., is added under an argon atmosphere a solution of 4-tert-butyl-3-methoxy-benzoic acid methyl ester (2.60 g, 11.7 mmol) in CH2Cl2 (65 mL). The reaction is warmed to room temperature and stirring is continued overnight. Another aliquot of BBr3 (1.13 mL, 11.7 mmol) is added, and the mixture is stirred for 6 hrs at ambient temperature before quenching by careful addition of water. The aqueous layer is extracted with CH2Cl2, the combined organics are washed with 1N aqueous NaOH, dried (Na2SO4) and concentrated. Purification by flash chromatography on silica gel (eluents: CH2Cl2 100%, then CH2Cl2/acetone 97:3) gives the title compound as yellowish solid. MS: 209.0 [M+H]+. tR (HPLC, Nucleosil C18HD column, 5-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 5.37 min. 1H-NMR (CDCl3): δ 1.46 (s, 9H), 3.94 (s, 3H), 5.60 (s, 1H), 7.36 (dd, 1H), 7.50 (d,1H), 7.57 (dd,1H) ppm.

Workup

  1. stirringthe mixture is stirred for 6 hrs at ambient temperature
  2. custombefore quenching by careful addition of water
  3. extractionThe aqueous layer is extracted with CH2Cl2
  4. washthe combined organics are washed with 1N aqueous NaOH
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica gel (eluents

Sources & evidence

ORD record
ord-1b7d6c12b5d24ffaa1cb6e5c0eb12c70
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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