Ethyl pyruvate → 4,6-di-tert-butyl-1H-indole-2-carboxylic acid ethyl ester

HRID 74467

Reaction equation

HRID 74467 reaction equation
C(=N[NH:15][C:16]1[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:19]=[C:18]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:17]=1)(C1C=CC=CC=1)C1C=CC=CC=1.[C:30]([O:35][CH2:36][CH3:37])(=[O:34])[C:31]([CH3:33])=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C(O)C.O>[CH2:36]([O:35][C:30]([C:31]1[NH:15][C:16]2[C:17]([CH:33]=1)=[C:18]([C:26]([CH3:27])([CH3:28])[CH3:29])[CH:19]=[C:20]([C:22]([CH3:25])([CH3:23])[CH3:24])[CH:21]=2)=[O:34])[CH3:37]

Participants

7

Reactant 4

HCID 12041Ethyl pyruvateHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 86669219N-benzhydrylidene-N'-(3,5-di-tert-butyl-phenyl)-hydrazine

Product 1

HCID 680050974,6-di-tert-butyl-1H-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

N-Benzhydrylidene-N′-(3,5-di-tert-butyl-phenyl)-hydrazine (617 mg, 1.6 mmol) was dissolved in ethanol (12 ml). Then, ethyl pyruvate (212 μl, 1.9 mmol) and p-toluene sulfonic acid monohydrate (914 mg, 4.8 mmol) were added thereto. This was heated and stirred at 150° C. by microwave under a nitrogen atmosphere for one hour. After cooling it to room temperature, the reaction mixture was combined with water and an aqueous solution saturated with sodium bicarbonate. The product was extracted into ethyl acetate. The organic layer was isolated, and washed with an aqueous solution saturated with sodium chloride, and dried over magnesium sulfate. The desiccant was removed by filtration, and concentration was performed. Then, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate=100/5). Thus, 4,6-di-tert-butyl-1H-indole-2-carboxylic acid ethyl ester was obtained as a brown solid (268 mg, 56%).

Workup

  1. temperatureThis was heated
  2. temperatureAfter cooling it to room temperature
  3. extractionThe product was extracted into ethyl acetate
  4. customThe organic layer was isolated
  5. washwashed with an aqueous solution saturated with sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. customThe desiccant was removed by filtration, and concentration
  8. customThen, the residue obtained by concentration under reduced pressure
  9. customwas purified by silica gel column chromatography (hexane/ethyl acetate=100/5)

Sources & evidence

ORD record
ord-3080e2058de345b89d9a39c24730ff71
Source dataset
uspto-grants-2014_09
Patent number
US08829199B2

Linked notes

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