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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence