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

HRID 2217087Notes

Reaction equation

HRID 2217087 reaction equation
CC([O-])(C)C.[K+].[CH3:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1.C(O)(=O)C.C(=O)CC.C[N:26]1C(=O)[CH2:29][CH2:28][CH2:27]1>CCCCCCC.O>[CH3:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1.[CH3:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([N:26]=[CH:27][CH2:28][CH3:29])[CH:9]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 527PropanalHCID 6736SkatoleHCID 13387N-methyl-2-pyrrolidoneHCID 23665647Potassium tert-butoxide2×

Product 2

HCID 6736SkatoleHCID 688630783-Methyl-N-propylidene-1H-indol-1-amineYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 10 kg (76.2 mol) 3-methylindole in 50 kg NMP is prepared, and add an initial amount of 0.08–0.12 eq. KOtBu-solution to the 3-methylindole solution. The HOSA and the KOtBu solutions are added over a period of 120 min simultaneously and proportionally over mass flow meters at 20° C. to the reaction mixture. After the addition is completed, add to the resulting dark brown suspension 6.9 L (381 mol) water, 13.7 kg (228.6 mol) acetic acid (100%) and 7.5 kg (129.2 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 248 L water and 42 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 3-times with 42 kg n-heptane. The combined organic phases are washed two times with 63 L water. The resulting brown heptane-solution is evaporated to dryness. This results in 11.6–12.5 kg 3-methyl-N-(propylidene)-1H-indol-1-amine (yield 81–90%) as a brown liquid.

Workup

  1. additionadd an initial amount of 0.08–0.12 eq
  2. customat 20° C.
  3. additionAfter the addition
  4. customuntil completion of the reaction
  5. customUnwanted salts precipitate from the reaction mixture
  6. filtrationThe resulting suspension is filtered
  7. customthe phases are separated
  8. extractionThe water phase is again extracted
  9. washThe combined organic phases are washed two times with 63 L water
  10. customThe resulting brown heptane-solution is evaporated to dryness

Sources & evidence

ORD record
ord-99068f3b3bb14426a8494848f3e88ca3
Source dataset
uspto-grants-2006_09
Patent number
US07112682B2

Reaction notes

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