Dimethylformamide → 4-Amino-3,5-dimethoxybenzoic acid

HRID 1165303Notes

Reaction equation

HRID 1165303 reaction equation
[CH3:1][O-:2].[Na+].Br[C:5]1[CH:6]=[C:7]([CH:11]=[C:12](Br)[C:13]=1[NH2:14])[C:8]([OH:10])=[O:9].CN(C)[CH:18]=[O:19]>[Cu-]=O.CO>[NH2:14][C:13]1[C:12]([O:2][CH3:1])=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][C:5]=1[O:19][CH3:18]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 10942334Sodium Methoxide2×HCID 119590494-amino-3,5-dibromobenzoic acid

Product 1

HCID 124090914-Amino-3,5-dimethoxybenzoic acidYield 88%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
5 °C

Procedure

258 g of copper(I) oxide and 1670 ml of sodium methylate solution (30% in methanol) were boiled at reflux (88°-93° C.) for 15 minutes while stirring and gassing with argon. At this temperature, there was added dropwise with simultaneous distillation a solution consisting of 531 g of 3,5-dibromo-4-aminobenzoic acid, 1670 ml of sodium methylate solution (30% in methanol) and 2700 ml of dimethylformamide (dried over molecular sieve). The solvent was subsequently further distilled. 2200 ml were distilled off in total. The resulting red suspension was stirred at 113°-114° C. for an additional 45 minutes. Thereafter, 1300 ml of dimethylformamide were distilled off in a water-jet vacuum. 7500 ml of 4N sodium hydroxide solution were added to the resulting red residue and the suspension was stirred at about 100° C. for 30 minutes. Thereby 800 ml were again distilled off. The hot suspension was suction filtered over an internal glass suction filter. The residue was suspended three times in 1800 ml of hot water and filtered off each time. The solution, cooled to 5° C., was adjusted to PH 5 with 2000 ml of acetic acid while stirring. The resulting brown suspension was suction filtered and the residue was washed with 1000 ml of ice-water. The residue was dried at 60° C. in a water-jet vacuum. The thus-obtained crude product was boiled up with 3200 ml of methanol. The brown suspension was suction filtered and the filtrate was evaporated to dryness. There were obtained 313 g (88%) of 4-amino-3,5-dimethoxybenzoic acid.

Workup

  1. temperatureat reflux (88°-93° C.) for 15 minutes
  2. additionAt this temperature, there was added dropwise with simultaneous distillation a solution
  3. distillation2200 ml were distilled off in total
  4. stirringThe resulting red suspension was stirred at 113°-114° C. for an additional 45 minutes
  5. distillationThereafter, 1300 ml of dimethylformamide were distilled off in a water-jet vacuum
  6. addition7500 ml of 4N sodium hydroxide solution were added to the resulting red residue
  7. stirringthe suspension was stirred at about 100° C. for 30 minutes
  8. distillationThereby 800 ml were again distilled off
  9. filtrationfiltered over an internal glass suction
  10. filtrationfilter
  11. filtrationfiltered off each time
  12. stirringwhile stirring
  13. filtrationsuction filtered
  14. washthe residue was washed with 1000 ml of ice-water
  15. dry with materialThe residue was dried at 60° C. in a water-jet vacuum
  16. customThe thus-obtained crude product
  17. filtrationsuction filtered
  18. customthe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-99d71ac0e6b34ea3a4a24b13f9dbd080
Source dataset
uspto-grants-1990_03
Patent number
US04908470

Reaction notes

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