Iodoethane → 1-Ethyl-3-methyl-1H-indole-5-carboxaldehyde

HRID 615956Notes

Reaction equation

HRID 615956 reaction equation
[O-:1][CH2:2][CH3:3].C(I)C.[CH2:7]([N:9]1[C:17]2[C:12](=[CH:13]C=[CH:15][CH:16]=2)[C:11]([CH3:18])=[CH:10]1)[CH3:8].[OH-].[Na+]>CN(C)C=O.O.C(OCC)C>[CH2:7]([N:9]1[C:17]2[C:12](=[CH:13][C:3]([CH:2]=[O:1])=[CH:15][CH:16]=2)[C:11]([CH3:18])=[CH:10]1)[CH3:8]

Participants

8

Reactant 4

HCID 6340IodoethaneHCID 14798Sodium HydroxideHCID 1194401-Hydroxyethyl radicalHCID 11182766HCID 11182766, compound

Product 1

HCID 203706741-Ethyl-3-methyl-1H-indole-5-carboxaldehydeYield 50%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

Into a 2000 milliliter 3 neck flask equipped with a magnetic stirring bar, a thermometer and a nitrogen inlet tube are introduced 400 milliliters anhydrous dimethylformamide, 220 milliliters anhydrous ethylether and 29.36 grams (0.22 moles) 3-methylindolyl (available from Aldrich Chemical Company). After the contents of this flask are thoroughly combined, about 64.84 grams (0.26 moles) thallous ethoxide are added to the solution, and the flask thereafter heated to 40° C with stirring for about 60 minutes during which time the reaction mixture takes on a metallic appearance. At the end of this interval, 41.33 grams (0.26 moles) ethyliodide is introduced into the flask whereupon precipitation of orange colored particulates takes place. The reaction mass is heated to a temperature of about 50° - 5° C with constant agitation for an additional 3 hours, cooled and the solids separated from the reaction mass by filtration. The filtrate is diluted with water and separates into 2 distinct phases; the ether phase being set aside and the aqueous phase being extracted several times with chloroform. All organic layers are then recombined and extracted several times with water to remove residual traces of dimethylformamide. The ether phase is now dried over anhydrous magnesium sulfate and evaporated to an oily residue. This residue is distilled at 80° C (0.2 mm) and the fraction collected at this temperature analyzed and found to be N-ethyl-3-methylindole. Into a 3 neck 250 milliliter round bottom flask equipped with a nitrogen inlet tube, a magnetic stirring bar and a thermometer are placed 17.47 milliliters dimethyformamide. The flask and its contents are cooled in an ice bath and 21.29 milliliters of POC13 added by dropwise addition. The flask is now transferred to a room temperature oil bath and 36.6 grams (0.23 moles) N-ethyl-3-methylindole in 25 milliliters dimethylformamide added by dropwise addition. The reaction of these materials is highly exothermic and the temperature of the bath is maintained at 40° C during the combination of these materials and the reaction allowed to proceed for an additional 3 hours at this temperature. At the end of this period, the reaction mixture is poured into about 1 liter of water with stirring, and the resulting solution titrated with sodiumhydroxide until slightly basic (approximately 7 milliliters base added to this solution). An oily residue product which forms is extracted with chloroform, the chloroform evaporated and the product purified by vacuum distillation; yield is approximately 50 percent.

Workup

  1. customAfter the contents of this flask are thoroughly combined
  2. temperatureThe reaction mass is heated to a temperature of about 50° - 5° C with constant agitation for an additional 3 hours
  3. temperaturecooled
  4. customthe solids separated from the reaction mass by filtration
  5. additionThe filtrate is diluted with water
  6. extractionthe aqueous phase being extracted several times with chloroform
  7. extractionextracted several times with water
  8. customto remove residual traces of dimethylformamide
  9. dry with materialThe ether phase is now dried over anhydrous magnesium sulfate
  10. customevaporated to an oily residue
  11. distillationThis residue is distilled at 80° C (0.2 mm)
  12. customthe fraction collected at this temperature
  13. customInto a 3 neck 250 milliliter round bottom flask equipped with a nitrogen inlet tube, a magnetic stirring bar
  14. temperatureThe flask and its contents are cooled in an ice bath
  15. addition21.29 milliliters of POC13 added by dropwise addition
  16. customis now transferred to a room temperature
  17. customThe reaction of these materials
  18. temperaturethe temperature of the bath is maintained at 40° C during the combination of these materials
  19. waitto proceed for an additional 3 hours at this temperature
  20. stirringwith stirring
  21. additionadded to this solution)
  22. extractionAn oily residue product which forms is extracted with chloroform
  23. customthe chloroform evaporated
  24. distillationthe product purified by vacuum distillation

Sources & evidence

ORD record
ord-f09efac2f8e14a84b6c4de46931c15e3
Source dataset
uspto-grants-1978_02
Patent number
US04072519

Reaction notes

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