Sulfuric Acid → (4-(Ethoxymethyl)-2,6-dimethoxyphenyl)boronic acid

HRID 1454114Notes

Reaction equation

HRID 1454114 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[C:8](Br)=[C:7]([O:14][CH3:15])[CH:6]=1)[CH3:2].C([Li])CCC.[B:21](OC)([O:24]C)[O:22]C.S(=O)(=O)(O)O>O1CCCC1>[CH2:1]([O:3][CH2:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([B:21]([OH:24])[OH:22])=[C:7]([O:14][CH3:15])[CH:6]=1)[CH3:2]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8470Trimethyl borateHCID 668796444-Bromo-3,5-dimethoxybenzyl ethyl etherHCID 178418339Butyllithium

Product 1

HCID 10236170(4-(Ethoxymethyl)-2,6-dimethoxyphenyl)boronic acidYield 81.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen atmosphere, to a solution of 4-bromo-3,5-dimethoxybenzyl ethyl ether (440.0 g) in tetrahydrofuran (4.0 L) was added dropwise n-butyl lithium (1.6 M n-hexane solution, 1.1 L) at −60° C. After stirring for 15 minutes at the same temperature, trimethyl borate (249.3 g) was added. The temperature of the mixture was gradually elevated, followed by stirring for 1 hour under ice-cooling. To the mixture was added dropwise 10% aqueous sulfuric acid solution (835 g). The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated aqueous NaCl solution. After drying over magnesium sulfate, the solvent was removed in vacuo. The residue was dissolved in isopropyl ether with heating and cooled. The crystalline precipitates were collected by filtration and dried to yield 4-ethyoxymethyl-2,6-dimetoxyphenylboronic acid (312.9 g).

Workup

  1. additionwas added
  2. temperaturecooling
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with water and saturated aqueous NaCl solution
  5. dry with materialAfter drying over magnesium sulfate
  6. customthe solvent was removed in vacuo
  7. dissolutionThe residue was dissolved in isopropyl ether
  8. temperaturewith heating
  9. temperaturecooled
  10. customThe crystalline precipitates
  11. filtrationwere collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-2276fed86ec5462a8ecb3516cf364ae8
Source dataset
uspto-grants-2009_01
Patent number
US07476758B2

Reaction notes

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