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

HRID 2217088Notes

Reaction equation

HRID 2217088 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.O.C(O)C>[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-amineYield 96%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent4×HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
30 °C

Procedure

In a 800 L vessel, prepare a solution of 3.0 kg (74.4 mol) sodium borohydride and 26.8 kg (124 mol, 86% purity) 3-methyl-N-(propylidene)-1H-indol-1-amine in 108 kg NMP. Prepare a solution of 4.5 kg (74.4 mol) glacial acetic acid in 27 kg NMP. Add the acetic acid solution over a period of about 30 nm at 30° C. to the sodium borohydride solution. Immediately hydrogen is evolved. Stir the reaction mixture at 30° C. until completion of the reaction (˜1 h). Add 6.3 kg ethanol to the reaction mixture, foaming occurs immediately. The reaction mixture is then worked-up by adding additional 80 L water cautiously. Attention is taken during the addition of water such that foaming is controlled, slow addition of water is recommended especially in the beginning to avoid uncontrolled foaming. Care is taken to ensure no or only minimal foaming occurs while the first 1–2 L of water is added. The reaction mixture is allowed to stand over night. Extract the water phase three times with 45 kg n-heptane and wash the combined organic phases with 66 L water. Evaporate the combined organic phases to dryness. This results in 22.4 kg 3-methyl-N-propyl-1H-indol-1-amine (yield 90%, 94% purity) as a brown liquid.

Workup

  1. customuntil completion of the reaction (˜1 h)
  2. additionis added
  3. waitto stand over night
  4. extractionExtract the water phase three times with 45 kg n-heptane
  5. washwash the combined organic phases with 66 L water
  6. customEvaporate the combined organic phases to dryness

Sources & evidence

ORD record
ord-cfa297d152bc4aef9f8cb3d3b4cedcd4
Source dataset
uspto-grants-2006_09
Patent number
US07112682B2

Reaction notes

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