Dimethyl Sulfate → 3-Bromo-2,5-difluoro-4-methoxybenzaldehyde

HRID 2212595Notes

Reaction equation

HRID 2212595 reaction equation
[Br:1][C:2]1[C:3]([F:12])=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[OH:10])[CH:5]=[O:6].[C:13](=O)([O-])[O-].[K+].[K+].COS(OC)(=O)=O.C(OC(=O)C)C>CN(C=O)C>[Br:1][C:2]1[C:3]([F:12])=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[O:10][CH3:13])[CH:5]=[O:6]

Participants

6

Reactant 4

HCID 6497Dimethyl SulfateHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 219664683-Bromo-2,5-difluoro-4-hydroxybenzaldehyde

Product 1

HCID 219664313-Bromo-2,5-difluoro-4-methoxybenzaldehydeYield 53,666%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromo-2,5-difluoro-4-hydroxybenzaldehyde (48.4 g, 0.193 mmol) in DMF (200 mL) was added potassium carbonate (40.0 g) and dimethylsulfate (27.4 mL). The reaction mixture was stirred at room temperature overnight. The reaction was diluted wit ethylacetate and washed successively with water and brine, dried over magnesium sulfate, filtered and evaporated. The residue was triturated with hexane to afford 26 g of 3-bromo-2,5-difluoro-4-methoxy benzaldehyde. The mother liquor was evaporated and chromatographed on silica gel (0–10% ethyl acetate in hexane) to give 10.86 g of more product. (38% overall yield from 2,5-dinitrophenol).

Workup

  1. washwashed successively with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was triturated with hexane

Sources & evidence

ORD record
ord-c80210c2957f425796ba0b687f48b6f0
Source dataset
uspto-grants-2006_09
Patent number
US07102000B2

Reaction notes

Loading…