Dimethylformamide → 3-Chloro-5-methoxybenzaldehyde

HRID 917291Notes

Reaction equation

HRID 917291 reaction equation
Cl[C:2]1[CH:3]=[C:4]([O:9][CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Mg].CN(C)[CH:14]=[O:15].CCOC(C)=O>C1COCC1.BrCCBr>[Cl:8][C:6]1[CH:7]=[C:2]([CH:3]=[C:4]([O:9][CH3:10])[CH:5]=1)[CH:14]=[O:15]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 365883,5-DichloroanisoleHCID 5462224Magnesium

Product 1

HCID 219046333-Chloro-5-methoxybenzaldehydeYield 54%

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

3,5-Dichloroanisole (74.0 g, 419 mmol) in THF (200 mL) was added dropwise to magnesium metal (14.2 g, 585 mmol, pre-washed with 0.5 N HCl) in THF (100 mL) at 25° C. After the addition, 1,2-dibromoethane (3.9 g, 20.8 mmol) was added dropwise. The resultant dark brown mixture was heated at reflux for 3 h. The mixture was cooled to 0° C., and N,N-dimethylformamide (60 mL) was added in one portion. The mixture was partitioned with diethyl ether (3×400 mL) and 6N HCl (500 mL). The combined organic extracts were washed with brine (300 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash chromatography (2×) on silica gel eluting with Hex:EtOAc (4:1) afforded the sub-title compound (38.9 g, 54%) as a yellow oil.

Workup

  1. additionwas added dropwise
  2. temperatureThe resultant dark brown mixture was heated
  3. temperatureat reflux for 3 h
  4. customThe mixture was partitioned with diethyl ether (3×400 mL) and 6N HCl (500 mL)
  5. washThe combined organic extracts were washed with brine (300 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give an oil

Sources & evidence

ORD record
ord-182e0063363b499a9ec7c09be2e48e2c
Source dataset
uspto-grants-2007_09
Patent number
US07273858B2

Reaction notes

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