Dimethylformamide dimethyl acetal → 3-Amino-4-(2,2-dimethoxyethyl)benzamide

HRID 494916Notes

Reaction equation

HRID 494916 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:7]([NH2:9])=[O:8])([O-])=O.[CH3:14][O:15][CH:16]([O:20][CH3:21])N(C)C.[H][H]>CN(C)C=O>[NH2:1][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[CH2:13][CH:16]([O:20][CH3:21])[O:15][CH3:14])[C:7]([NH2:9])=[O:8]

Participants

5

Reactant 3

HCID 78373Dimethylformamide dimethyl acetalHCID 87896Benzamide, 4-methyl-3-nitro-HCID 178418361HCID 178418361, compound

Product 1

HCID 576827803-Amino-4-(2,2-dimethoxyethyl)benzamideYield 47.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

19.5 g of 3-nitro-4-methylbenzamide and 30 g of dimethylformamide dimethyl acetal were dissolved in 200 ml of dimethylformamide. The obtained mixture was stirred at 140° C. for 20 hours. The mixture was then concentrated under a reduced pressure. Thereafter, 360 ml of methanol and 25 g of chlorotrimethylsilane were added to the residue. The obtained solution was heated to reflux for 16 hours. The reaction solution was cooled and then concentrated under a reduced pressure. Water and ethyl acetate were added thereto, so as to divide an organic layer. The organic layer was separated, and then washed with a saturated sodium bicarbonate aqueous solution and a saturated sodium chloride solution. It was then dried over anhydrous magnesium sulfate. The mixture was filtered through 100 g of a silica gel layer, and then washed with ethyl acetate. Thereafter, the filtrate was concentrated under a reduced pressure. 0.9 g of 10% palladium carbon was added to 150 ml of a methanol solution containing the obtained crude product, and the mixture was intensively stirred in a hydrogen atmosphere. After completion of the reaction, the catalyst was removed by filtration, and the filtrate was concentrated under a reduced pressure. The obtained residue was purified by NH silica gel column chromatography (hexane/ethyl acetate), so as to obtain 11.5 g of the subject compound.

Workup

  1. concentrationThe mixture was then concentrated under a reduced pressure
  2. additionThereafter, 360 ml of methanol and 25 g of chlorotrimethylsilane were added to the residue
  3. temperatureThe obtained solution was heated
  4. temperatureto reflux for 16 hours
  5. temperatureThe reaction solution was cooled
  6. concentrationconcentrated under a reduced pressure
  7. additionWater and ethyl acetate were added
  8. customThe organic layer was separated
  9. washwashed with a saturated sodium bicarbonate aqueous solution
  10. dry with materialIt was then dried over anhydrous magnesium sulfate
  11. filtrationThe mixture was filtered through 100 g of a silica gel layer
  12. washwashed with ethyl acetate
  13. concentrationThereafter, the filtrate was concentrated under a reduced pressure
  14. addition0.9 g of 10% palladium carbon was added to 150 ml of a methanol solution
  15. additioncontaining the
  16. customobtained crude product
  17. customAfter completion of the reaction
  18. customthe catalyst was removed by filtration
  19. concentrationthe filtrate was concentrated under a reduced pressure
  20. customThe obtained residue was purified by NH silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-6de73e576d034d3393745071b94d85e4
Source dataset
uspto-grants-2009_05
Patent number
US07538123B2

Reaction notes

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