Acetic Acid → 3-Methyl-N-propyl-1H-indol-1-amine

HRID 2217089Notes

Reaction equation

HRID 2217089 reaction equation
[BH4-].[Na+].[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([N:13]=[CH:14][CH2:15][CH3:16])[CH:5]=1.C(O)(=O)C.[H][H]>CN1C(=O)CCC1.CCCCCCC.O>[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([NH:13][CH2:14][CH2:15][CH3:16])[CH:5]=1

Participants

8

Reactant 4

HCID 176Acetic Acid2×HCID 4311764Sodium borohydride2×HCID 688630783-Methyl-N-propylidene-1H-indol-1-amineHCID 178418361HCID 178418361, compound

Product 1

HCID 219460633-Methyl-N-propyl-1H-indol-1-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8900HeptaneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
30 °C

Procedure

Prepare a solution of sodium borohydride (4.54 kg, 120 mol) in 38 kg of NMP. Add to this solution, a solution of 3-methyl-N-(propylidene)-1H-indol-1-amine (38.6 kg, 190 mol) in 78 kg of n-heptane. Prepare a solution of 6.8 kg (120 mol) glacial acetic acid in 32 kg n-heptane. Add the acetic acid solution over a period of about 30 min at 30° C. to the sodium borohydride solution using a pump. Immediately hydrogen evolution occurs. Rinse the pump with 3 kg n-heptane and add the rinse to the reaction mixture. Stir the reaction mixture at 30° C. until completion of the reaction (˜1 h). The reaction mixture is then worked-up by adding 76 L water. No or only minimal foaming is observed during the addition of water. Stir the mixture over night and separate the phases. Add 2.82 kg HCl (30%) and 4.75 kg water to the n-heptane phase, check the pH, if the pH is above 1, add more HCl. Heat this mixture to 75° C. internal temperature for ˜2 h. Cool the mixture to 25° C. in order to control the evolution of hydrogen. If no more residual hydrogen is evolved, adjust pH level to 7, add additional 30 kg water, separate the phases and wash the n-Heptane phase twice with 37 kg water. Evaporate the n-heptane phase to dryness. This results in 37.5 kg 3-methyl-N-propyl-1H-indol-1-amine (98%) as a brown liquid.

Workup

  1. additionAdd to this solution
  2. washRinse the pump with 3 kg n-heptane
  3. additionadd the
  4. washrinse to the reaction mixture
  5. customuntil completion of the reaction (˜1 h)
  6. stirringStir the mixture over night
  7. customseparate the phases
  8. additionAdd 2.82 kg HCl (30%) and 4.75 kg water to the n-heptane phase
  9. additionif the pH is above 1, add more HCl
  10. temperatureHeat this mixture to 75° C. internal temperature for ˜2 h
  11. temperatureCool the mixture to 25° C. in order
  12. additionadd additional 30 kg water
  13. customseparate the phases
  14. washwash the n-Heptane phase twice with 37 kg water
  15. customEvaporate the n-heptane phase to dryness
  16. customThis results in 37.5 kg 3-methyl-N-propyl-1H-indol-1-amine (98%) as a brown liquid

Sources & evidence

ORD record
ord-39a24462ce95491b921c751857bc3145
Source dataset
uspto-grants-2006_09
Patent number
US07112682B2

Reaction notes

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