Indole → HCID 23393853, compound

HRID 966483Notes

Reaction equation

HRID 966483 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:8])[CH2:4][C:5]([CH3:7])=O.[H][H].I[C:20]1[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[CH:23]=[CH:22][C:21]=1[NH2:29].N1C2C(=CC=CC=2)C=C1.[N+](C1C=CC(N)=CC=1)([O-])=O>[Cu]I.Cl>[CH2:10]([O:9][C:3]([C:4]1[C:20]2[C:21](=[CH:22][CH:23]=[C:24]([N+:26]([O-:28])=[O:27])[CH:25]=2)[NH:29][C:5]=1[CH3:7])=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

9

Reactant 6

HCID 798IndoleHCID 74754-NitroanilineHCID 24758Sodium hydrideHCID 142266Benzyl acetoacetateHCID 2226292-Iodo-4-nitroanilineHCID 178418361HCID 178418361, compound2×

Product 1

HCID 23393853HCID 23393853, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 313Hydrochloric AcidSolvent

Procedure

NaH (60% in oil) (1.75 g, 43.80 mmol, 2 eq) was washed with dry hexanes under nitrogen in the normal way to remove oil. The NaH and hexanes dispersion was stirred for 2 minutes. NaH was allowed to settle, and the supernatant liquid was removed with syringe. Repeated the washing operation with additional 20 mL hexanes. DMF (10 mL) was added to the reaction flask, covered the gray solid. benzyl acetoacetate (6.56 mL, 32.80 mmol, 1.5 eq) was added dropwise with syringe, at the same time, hydrogen was released. After several minutes, when the evolution of hydrogen was stopped, CuI (6.25 g, 32.80 mmol, 1.5 eq) was added to the yellow solution. The color of the solution changed to orange and then to brown. 2-Iodo-4-nitro-phenylamine (5.19 g, 21.9 mmol, 1.0 eq) was added to the brown solution, and the mixture was heated to 120° C.-130° C. in the heating control oil bath. The color of the reaction mixture further darkened as the temperature increased. The mixture was stirred for 16 hours, cooled to room temperature, poured into 1N HCl solution (100 mL), the aqueous solution was extracted with ethyl acetate (3×200 mL). Some precipitate went into the organic phase. The combined organic solution was dried over MgSO4, filtered and concentrated in vacuo to gave a dark brown oil which was purified by flash chromatography (SiO2, 60:40 hexanes-ethyl acetate) to yield the mixture of the desired indole and 4-nitroaniline (1.22 g) as a dark brown solid. The mixture was carried over to the next step.

Workup

  1. customto remove oil
  2. customthe supernatant liquid was removed with syringe
  3. additionDMF (10 mL) was added to the reaction flask
  4. waitAfter several minutes
  5. temperaturethe mixture was heated to 120° C.-130° C. in the heating control oil bath
  6. temperatureThe color of the reaction mixture further darkened as the temperature increased
  7. stirringThe mixture was stirred for 16 hours
  8. extractionthe aqueous solution was extracted with ethyl acetate (3×200 mL)
  9. dry with materialThe combined organic solution was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto gave a dark brown oil which
  13. customwas purified by flash chromatography (SiO2, 60:40 hexanes-ethyl acetate)
  14. customto yield

Sources & evidence

ORD record
ord-a7c2bedfd2b541e585bde02f1a012184
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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