Triethylamine → Tert-butyl 4-bromo-3-methylbenzoate

HRID 220824Notes

Reaction equation

HRID 220824 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].S(Cl)(Cl)=O.C(N(CC)CC)C.[CH3:23][C:24]([CH3:27])([O-])[CH3:25].[Li+]>C1(C)C=CC=CC=1>[C:24]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Br:1])=[C:3]([CH3:11])[CH:4]=1)([CH3:27])([CH3:25])[CH3:23]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 821314-Bromo-3-methylbenzoic acidHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

Product 1

HCID 11845988Tert-butyl 4-bromo-3-methylbenzoateYield 71.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-Bromo-3-methyl-benzoic acid (2.06 g, 9.6 mmol) and thionyl chloride (2.2 ml, 30.2 mmol) in toluene (50 ml) were heated at reflux for 2 h then concentrated in vacuo and azeotroped with toluene. The residue was dissolved in THF (100 ml) and triethylamine (2.8 ml, 20.1 mmol), cooled down to 0° C. and lithium tert-butoxide (1.24 g, 15.5 mmol) was added portionwise. The mixture was stirred for 18 h at room temperature then concentrated in vacuo. The residue was dissolved in EtOAc, washed with 1M HCl, saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 5% EtOAc:95% pet. ether) to yield the title compound (1.86 g, 71%).

Workup

  1. temperatureat reflux for 2 h
  2. concentrationthen concentrated in vacuo
  3. customazeotroped with toluene
  4. dissolutionThe residue was dissolved in THF (100 ml)
  5. concentrationthen concentrated in vacuo
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with 1M HCl, saturated NaHCO3
  8. dry with materialbrine, dried
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel (eluant; 5% EtOAc:95% pet. ether)

Sources & evidence

ORD record
ord-d4e3828955d7402586e89e92f84e40bf
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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