Dimethylformamide → 2-Formyl-3,5-dimethoxy-6-methylbenzoic acid methyl ester

HRID 1377839Notes

Reaction equation

HRID 1377839 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH3:11][O:12][C:13](=[O:25])[C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([O:22][CH3:23])[C:15]=1[CH3:24]>ClCCl>[CH3:11][O:12][C:13](=[O:25])[C:14]1[C:15]([CH3:24])=[C:16]([O:22][CH3:23])[CH:17]=[C:18]([O:20][CH3:21])[C:19]=1[CH:3]=[O:4]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 11790477Benzoic acid, 3,5-dimethoxy-2-methyl-, methyl ester

Product 1

HCID 540645902-Formyl-3,5-dimethoxy-6-methylbenzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 340 ml of N,N-dimethylformamide in 1 l of dichloromethane were added slowly 404 ml of phosphoryl chloride. The solution was stirred for 1.5 h at room temperature, and then, a solution of 618 g of 3,5-dimethoxy-2-methylbenzoic acid methyl ester in 200 ml of dichloromethane was added within 10 min. The mixture was heated for 72 h at reflux temperature. After cooling, the mixture was slowly poured into 3 l of ice-water and subsequently extracted with 3.6 l of dichloromethane. The organic layer was washed with 2 l of saturated sodium carbonate solution and twice with 2 l of water. The organic layer was dried over sodium sulfate and the solvent was evaporated in vacuo. The solid residue was triturated in 3 l of ethyl acetate at 60° C., and after cooling, 1.5 l of hexane were added. The solid was isolated by filtration to yield 646 g of 2-formyl-3,5-dimethoxy-6-methylbenzoic acid methyl ester, m.p. 164°-165° C.

Workup

  1. temperatureThe mixture was heated for 72 h
  2. temperatureat reflux temperature
  3. temperatureAfter cooling
  4. extractionsubsequently extracted with 3.6 l of dichloromethane
  5. washThe organic layer was washed with 2 l of saturated sodium carbonate solution and twice with 2 l of water
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customthe solvent was evaporated in vacuo
  8. customThe solid residue was triturated in 3 l of ethyl acetate at 60° C.
  9. temperatureafter cooling
  10. addition1.5 l of hexane were added
  11. customThe solid was isolated by filtration

Sources & evidence

ORD record
ord-3f9bfea05a124f468dfba3b3a452d633
Source dataset
uspto-grants-1997_09
Patent number
US05665746

Reaction notes

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