Acetic Acid → 1H-Indol-1-amine, N-propyl-

HRID 2217091Notes

Reaction equation

HRID 2217091 reaction equation
[BH4-].[Na+].[CH:3](=[N:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1)[CH2:4][CH3:5].C(O)(=O)C.[H][H]>CN1C(=O)CCC1.CCCCCCC.O>[CH2:3]([NH:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1)[CH2:4][CH3:5]

Participants

8

Reactant 4

HCID 176Acetic Acid2×HCID 4311764Sodium borohydride2×HCID 68862839N-propylidene-1H-indol-1-amineHCID 178418361HCID 178418361, compound

Product 1

HCID 107023901H-Indol-1-amine, N-propyl-

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8900HeptaneSolvent3×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
30 °C

Procedure

Prepare a solution of 0.83 kg (21.9 mol) sodium borohydride in 16.6 kg NMP. Add 31.9 kg N-(propylidene)-1H-indol-1-amine as a 19.7% solution in n-heptane (36.5 mol) and additional 7.7 kg n-Heptane. Prepare a solution of 1.32 kg (21.9 mol) glacial acetic acid in 2.8 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 will occur. Rinse the pump with 2 kg n-heptane. Stir the reaction mixture at 30° C. until completion of the reaction (˜1 h). The reaction mixture is then worked-up by adding 20 L water. No or only minimal foaming is observed during the addition of water. Stir the mixture over night and separate the phases. Add 0.9 kg HCl (30%) and 3.4 kg water to the n-heptane phase, check whether the pH is below 1. Add additional amounts of HCl if necessary to adjust the pH around 1. Heat this mixture to 75° C. internal temperature for ˜2 h. Cool the mixture to 25° C. in order to control the residual hydrogen that is evolved. If no more residual hydrogen is evolved, add additional 20.3 kg water, and adjust pH to a level >7 with NaOH (33%). Separate the phases and wash the n-heptane phase with 20.3 kg water. Evaporate the n-heptane phase to dryness. This results in 5.84 kg N-propyl-1H-indol-1-amine (82.6%) as a brown liquid.

Workup

  1. washRinse the pump with 2 kg n-heptane
  2. customuntil completion of the reaction (˜1 h)
  3. stirringStir the mixture over night
  4. customseparate the phases
  5. additionAdd 0.9 kg HCl (30%) and 3.4 kg water to the n-heptane phase
  6. additionAdd additional amounts of HCl if necessary
  7. temperatureHeat this mixture to 75° C. internal temperature for ˜2 h
  8. temperatureCool the mixture to 25° C. in order
  9. additionadd additional 20.3 kg water
  10. customSeparate the phases
  11. washwash the n-heptane phase with 20.3 kg water
  12. customEvaporate the n-heptane phase to dryness
  13. customThis results in 5.84 kg N-propyl-1H-indol-1-amine (82.6%) as a brown liquid

Sources & evidence

ORD record
ord-196cfbf63199449e96f02d467a042e60
Source dataset
uspto-grants-2006_09
Patent number
US07112682B2

Reaction notes

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