Acetic Acid → N-propylidene-1H-indol-1-amine

HRID 2217090Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CC([O-])(C)C.[K+].C(O)(=O)C.C(=O)CC.C[N:25]1C(=O)[CH2:28][CH2:27][CH2:26]1>CCCCCCC.O>[CH:26](=[N:25][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)[CH2:27][CH3:28]

Participants

Conditions

Temperature: 15 °C

Procedure

Prepare a solution of 6.4 kg (54.6 mol) indole in 25 kg NMP. Add to this solution the HOSA and the KOtBu solutions as prepared above over a period of 180 min simultaneously and proportionally over mass flow meters and maintain the reaction mixture at 15° C. After the addition is completed, add to the resulting dark brown suspension 4.3 L (239 mol) water, 9.7 kg (161.5 mol) acetic acid (100%) and 5.3 kg (91.3 mol) propionaldehyde. Stir the mixture at 20° C. for ˜1 h, until completion of the reaction. The reaction mixture is then worked-up by adding 180 L water and 21 kg n-heptane. Unwanted salts precipitate from the reaction mixture. The resulting suspension is filtered and the phases are separated. The water phase is again extracted 4-times with 21 kg n-heptane. The combined organic phases are washed two times with 45 L water. The resulting brown heptane-solution is evaporated to a 15–25% solution. This results in 6.3–7.0 kg N-(propylidene)-1H-indol-1-amine (yield 67–74%, corrected for 19.7–24.1% assay) as a brown liquid.

Workup

additionAdd to this solution the HOSA
additionAfter the addition
customuntil completion of the reaction
customUnwanted salts precipitate from the reaction mixture
filtrationThe resulting suspension is filtered
customthe phases are separated
washThe combined organic phases are washed two times with 45 L water
customThe resulting brown heptane-solution is evaporated to a 15–25% solution

Sources & evidence

ORD record: ord-28f5b78900ae4fb8b385f5f18b1652cc
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07112682B2

Reaction notes

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