Trimethyl orthoformate → 1-Bromo-2-(dimethoxymethyl)-4-methylbenzene

HRID 501714Notes

Reaction equation

HRID 501714 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:3]=1C=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:23][O:24][CH:25](OC)[O:26][CH3:27]>CO>[Br:1][C:2]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:3]=1[CH:25]([O:26][CH3:27])[O:24][CH3:23]

Participants

5

Reactant 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 118458962-Bromo-5-methylbenzaldehyde

Product 1

HCID 667049941-Bromo-2-(dimethoxymethyl)-4-methylbenzeneYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Step AI (3): 2-Bromo-5-methylbenzaldehyde (500 mg, 2.51 mmol) was dissolved in methanol (5.0 mL). p-Toluenesulfonic acid monohydrate (90 mg, 0.52 mmol) and trimethoxymethane (5 mL) were added. The reaction mixture was heated at reflux for 5 h. The reaction mixture was extracted with DCM and washed with saturated aqueous sodium bicarbonate. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuum to yield 1-bromo-2-(dimethoxymethyl)-4-methylbenzene (615 mg, 99%) as a colorless oil. LC-MS (M−OCH3)+=213.25. 1H NMR (CD3OD, 500 MHz) δ 7.41-7.39 (m, 2H) 6.98 (d, J=10 Hz, 1H) 5.51 (s, 1H) 3.37 (s, 6H) 2.30 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 h
  3. extractionThe reaction mixture was extracted with DCM
  4. washwashed with saturated aqueous sodium bicarbonate
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-12f13d8064ba4300a6cd10f9a520d680
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

Loading…