Synthesis of 5‐MeO-DMT via Fischer Indole

[WillD]

2-(5-Methoxy-1H-indol-3-yl)-N,N-dimethylethan-amine (5-Meo-DMT freebase).
1. To a clean and dry 5 L reactor was charged 4-methoxyphenylhydrazine hydrochloride (145.0 g; 0.83 mol, 1.0 equiv), followed by water (1.45 L, 10 vol) under a nitrogen atmosphere at 20−25 *C.
2. The contents of the reactor were then stirred at 30−35 *C and a dark red colored suspension was observed.
3. To the suspension, concentrated H2SO4 (47.7 ml, 0.91 mol, 1.1 equiv) was cautiously added dropwise under a nitrogen atmosphere over 10 min while maintaining the temperature below 40 *C (slightly exothermic).
4. The brown/red solution was heated to 35−40 *C (with a target temperature of 37 *C) and stirred for an additional 10 min.
5. A solution of 4,4-diethoxy-N,N-dimethyl-butan-1-amine (165.0 g, 0.87 mol, 1.05 equiv) was prepared in acetonitrile (0.58 L, 4.0 vol), and added dropwise to the reactor under a nitrogen atmosphere over approximately 60 min while maintaining the temperature between 35 and 40 *C.
6. The addition funnel was rinsed with acetonitrile (145 ml, 1.0 vol) and added dropwise to the reactor.
7. The temperature was maintained at 40 *C, and the contents were agitated for an additional 4 h.
8. The mixture was cooled to 20−25 *C and the contents were transferred to a 10 L reactor.
9. The acidic aqueous solution was washed with 2-MeTHF (2x2.03L, 14.0 vol).
10. After each wash, the layers were allowed to settle for 15 min.
11. The lower acidic aqueous layer was collected and the upper 2-MeTHF wash was discarded.
12. The acidic aqueous layer was recharged to the reactor and sodium hydroxide solution (4 M, 0.65 L, 4.5 vol) was added dropwise while maintaining the temperature at 20−25 *C to bring the pH to 11−12 providing a milky suspension.
13. The suspension was extracted with 2-MeTHF (3x1.45 L, 10.0 vol); following each extraction, the layers were allowed to settle for 15 min, the lower alkaline water layer was separated into a drum, and the upper organic layer was collected.
14. The lower aqueous layer was discarded and the combined 2-MeTHF organic layers were transferred to a 20 L-flask.
15. The solution was concentrated in vacuo to an oily amber residue.
16. Residual water was removed azeotropically by redissolving the residue with fresh 2-MeTHF (1.45 L, 10 vol) and repeating the concentration step.
17. This oily residue was dried on the rotatory evaporator under vacuum (10−20 mbar) for 1 h at 40−45 *C to provide 117.68 g (64.9% theoretical yield) of crude 5-MeO-DMT freebase.

 

[Octopusssss]

Hello

The bigest cost in this reaction is step number 5:

5. A solution of 4,4-diethoxy-N,N-dimethyl-butan-1-amine (165.0 g, 0.87 mol, 1.05 equiv) was prepared in acetonitrile (0.58 L, 4.0 vol), and added dropwise to the reactor under a nitrogen atmosphere over approximately 60 min while maintaining the temperature between 35 and 40 *C.

If 4,4-diethoxy-N,N-dimethyl-butan-1-amine can be replaced with some other common substance or chiper one than reaction will be much more cheaper and without complicated orders

 

[G.Patton]

Hello, unfortunately no. This substance only can give 5‐MeO-DMT via Fisher cyclization.

 

[Agilent1100DAD]

Doing this one today, I’ll post a photo.
What you see is the Fisher indole reaction (with the addition of 4,4 diethoxy-N,N/dimethyl-butan-1-amine in a solution of ACN to an acidic soln of 4-methoxyphenylhydrazine under an inert atm) in a highly ventilated room.

 

[Agilent1100DAD]

Update: when I added the 4M NaOH, a cloudy precipitate formed. I put the residue in a tray to evaporate off the 2-Me-THF. Even after 4 hours in a vacuum oven, I still couldn’t get rid of the solvent. I followed the last step which involves utilizing a roto vap at 40 C and at 10-20 mbar. I stored the oil in an amber vial and will leave it in the vac oven all day. I will post photos (bonus nacho photo). There is also another purification step involved, which is optional. Here it is:

(After the roto vap step)

-The crude freebase was dissolved in acetone (1.45 L, 10.0 vol) and poured through a pad of silica (230–400 mesh, 725 g, 5 wt).
-The pad was eluted with acetone/MeOH (9:1, v-v, 14.5 L, 100.0 vol).
-The combined filtrates were concentrated to provide 102.94 g of purified 5-MeO-DMT freebase (56.8% yield, 98.27% area by HPLC) as a pale clear orange oil that slowly solidified on standing.

I am waiting on some silica gel to arrive and I will attempt this additional purification step, after I successfully evaporate the solvent which is a pain in the ass so far.

 

[G.Patton]

Ty for nacho =)

 

[Joker_55555]

Synthesis of tryptamine from 4-chlorobutanal and phenyl hydrazine, Grandberg Reaction

Have any of your friends tried this method ??? Materials 10.8 g phenylhydrazine 10.6 g chlorobutyric aldehyde (4-chlorobutanal) ethyl alcohol 80% ethanol ether sodium sulfate benzene caustic soda 0.1 N hydrochloric acid Description of the method Solutions of 10.8 g (0.1 mol) of...

bbgate.com

Hello, possible to make mexamine and tryptamine using the Grandberg method This method should be easier and more efficient. Also, it does not use much solvent and the purification step is not difficult.