Ethyl orthoformate → 1-Bromo-2-(dimethoxymethyl)-4-methoxybenzene

HRID 501709Notes

Reaction equation

HRID 501709 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1C=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O[CH:27]([O:31][CH2:32]C)[O:28][CH2:29]C)C>CO>[Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:27]([O:28][CH3:29])[O:31][CH3:32]

Participants

5

Reactant 3

HCID 31214Ethyl orthoformateHCID 3444802-Bromo-5-methoxybenzaldehydeHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 151144041-Bromo-2-(dimethoxymethyl)-4-methoxybenzeneYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Step AH (2): 2-Bromo-5-methoxybenzaldehyde (1069 mg, 4.975 mmol) was dissolved in a mixture of methanol (20 mL) and triethylorthoformate (20 mL). p-Toluenesulfonic acid monohydrate (180.0 mg, 0.946 mmol) was added and the reaction mixture was stirred under reflux for 5 h. The reaction was quenched with aqueous NaHCO3 and extracted with DCM. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuum at the temperature, not exceeding 35° C. The residue was purified by silica gel chromatography to give 1-bromo-2-(dimethoxymethyl)-4-methoxybenzene (688.5 mg, 53%) as colorless oil. LC-MS (M+H)+=261.00. 1H NMR (CDCl3, 500 MHz) δ 7.42 (d, J=7.0 Hz, 1H) 7.16 (d, J=3.0 Hz, 1H) 6.76 (dd, J1=10 Hz, J2=3.0 Hz, 1H) 5.50 (s, 1H) 3.80 (s, 3H) 3.39 (s, 6H).

Workup

  1. temperatureunder reflux for 5 h
  2. customThe reaction was quenched with aqueous NaHCO3
  3. extractionextracted with DCM
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum at the temperature
  7. customexceeding 35° C
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-fa6d953bf0c7414bb3ca5df5c073390f
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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