Nitromethane → 5-(2-nitro-vinyl)-1H-indole

HRID 2386525Notes

Reaction equation

HRID 2386525 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)=O.CCOC(C)=O.CCCCCC.[N+:24]([CH3:27])([O-:26])=[O:25]>>[N+:24]([CH:27]=[CH:1][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)([O-:26])=[O:25]

Participants

5

Reactant 4

HCID 6375NitromethaneHCID 8058HexaneHCID 8857Ethyl AcetateHCID 589040Indole-5-carboxaldehyde

Product 1

HCID 544650165-(2-nitro-vinyl)-1H-indoleYield 11%

Procedure

5-Formyl indole (14.5 g) was refluxed with NH4OAc (10.0 g) in nitromethane ((100 mL) for 3 hours. The mixture was cooled and evaporated under reduced pressure. The residue was recrystallized from isopropanol to give the first portion of intermediate and the mother liquid was purified by chromatograph (EtOAc:hexane=1:4 to 2:3) to the second portion intermediate of 5-(2-nitro-vinyl)-1H-indole (2.09 g combined, in 11% yield), which was treated with NaBH4 (1.85 g) in methanol (150 mL) at room temperature for 35 min then quenched with acetic acid (4 mL), concentrated and followed by chromatography purification (EtOAc:hexane=1:9) to afford 5-(2-nitro-ethyl)-1H-indole (1.37 g) in 65% yield. This nitro compound was hydrogenated with Pd—C (10%) under atmosphere hydrogen in methanol overnight to afford 2-(1H-indol-5-yl)-ethylamine in 99% yield. LC-MS showed the product had the expected M+H+ of 161.

Workup

  1. temperatureThe mixture was cooled
  2. customevaporated under reduced pressure
  3. customThe residue was recrystallized from isopropanol
  4. customto give the first portion of intermediate

Sources & evidence

ORD record
ord-4131d20f3cda487899b1529c92955d01
Source dataset
uspto-grants-2012_09
Patent number
US08268822B2

Reaction notes

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