Acetic Acid → Methyl 3-amino-4-(tert-butyl)benzoate

HRID 1637487Notes

Reaction equation

HRID 1637487 reaction equation
C(O)(=O)C.[C:5]([C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[N+:19]([O-])=O)([CH3:8])([CH3:7])[CH3:6]>CO.C(OCC)(=O)C.CCCCCC.[Zn]>[C:5]([C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[NH2:19])([CH3:8])([CH3:6])[CH3:7]

Participants

7

Reactant 2

HCID 176Acetic Acid2×HCID 19348444Methyl 4-t-butyl-3-nitrobenzoate

Product 1

HCID 11959027Methyl 3-amino-4-(tert-butyl)benzoateYield 85%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalyst2×HCID 887MethanolSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

40 g of zinc powder and 8 ml of acetic acid were added to a solution of 22.7 g of methyl 4-t-butyl-3-nitrobenzoate (prepared as described in Preparation 4) in 400 ml of methanol, and the resulting mixture was stirred for 40 minutes. At the end of this time, a further 26.6 g of zinc powder were added (making a total amount of 66.6 g or 1.02 mmol). 20 ml of acetic acid were then added dropwise over a period of 1.5 hours to the mixture, and the resulting mixture was stirred for 2 hours. At the end of this time, the reaction mixture was diluted with a 10:1 by volume mixture of ethyl acetate and hexane, and the diluted mixture was filtered, using a Celite (trade mark) filter aid. The filtrate was concentrated by evaporation under reduced pressure, and the concentrate was dissolved in ethyl acetate. The resulting solution was washed twice with a saturated aqueous solution of ammonium chloride, once with a saturated aqueous solution of sodium hydrogencarbonate and once with water. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 150 g of silica gel, using a gradient elution method, with mixtures of hexane and ethyl acetate ranging from 30:1 to 4:1 as the eluent, to give 16.5 g of the title compound as an oily substance, that is an 85% yield based on the starting material used in Preparation 4.

Workup

  1. stirringthe resulting mixture was stirred for 2 hours
  2. filtrationthe diluted mixture was filtered
  3. filtrationfilter aid
  4. concentrationThe filtrate was concentrated by evaporation under reduced pressure
  5. dissolutionthe concentrate was dissolved in ethyl acetate
  6. washThe resulting solution was washed twice with a saturated aqueous solution of ammonium chloride, once with a saturated aqueous solution of sodium hydrogencarbonate and once with water
  7. customThe solvent was removed by distillation under reduced pressure
  8. customthe resulting residue was purified by column chromatography through 150 g of silica gel
  9. washa gradient elution method

Sources & evidence

ORD record
ord-e67198587cb440a08f1c21c4baf005bf
Source dataset
uspto-grants-2000_03
Patent number
US06040339

Reaction notes

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