LSD synthesis from lysergic acid via PyBOP

[Nicoino]

Will the hydrated form of LA work the same or it has to be dried?

 

[psy]

Will the hydrated form of LA work the same or it has to be dried?

NicoinoIt has to be dried. Drying LA is pretty easy though. Just heat and a strong vacuum.

 

[Nicoino]

It has to be dried. Drying LA is pretty easy though. Just heat and a strong vacuum.

psyI report anhydrous condition aren't needed

 

[Molecula25]

Hi guys, does anyone know about hydrolysis of ergotamine with sodium dithionite and KOH?

 

[psy]

Hi guys, does anyone know about hydrolysis of ergotamine with sodium dithionite and KOH?
View attachment 21428

Molecula25Why would you use dithionite? You are trying to hydrolyze it, not reduce it. You have 2 double bonds that could certainly get reduced, and how are you suppose to get a pH of 5 with KOH?

 

[Nicoino]

Why would you use dithionite? You are trying to hydrolyze it, not reduce it. You have 2 double bonds that could certainly get reduced, and how are you suppose to get a pH of 5 with KOH?

psyFew mg of dithionite are used in some patents as antioxidant.

 

[The Alchemist]

This topic seems majorly underrated. It seems downright revolutionary compared to how I learned to make it.

I read an exchange where someone suggested the methyl ester could racemize during hydrolysis. Is this a concern with the entiopure d isomer? I notice TLC is not included in the work up.

Is a rotovap really optional? This method to be approaching bathtub synthesis without it. No heat? This sounds simpler than mdma or amphetamine.

What am I missing here? Do we work under yellow or red light? What are the major complications? Does the final product yeild isolsd at all?

 

[Nicoino]

This topic seems majorly underrated. It seems downright revolutionary compared to how I learned to make it.

I read an exchange where someone suggested the methyl ester could racemize during hydrolysis. Is this a concern with the entiopure d isomer? I notice TLC is not included in the work up.

Is a rotovap really optional? This method to be approaching bathtub synthesis without it. No heat? This sounds simpler than mdma or amphetamine.

What am I missing here? Do we work under yellow or red light? What are the major complications? Does the final product yeild isolsd at all?

The AlchemistGet reasonably pure LA is a pain in the ass, nearly all the hydrolysis lead to brown/black product which as to be purified.
Even with good quality LA the coupling reaction mixture gets brown black and the work up is not as simple as it is stated (maybe if you start with 100% pure precursors, solvents degassed and professional equipment you have a small change of not happening, but for the home chemist dark solution has to be expected).
Purification of the product is no joke if you don't have access to column chromatography or if you don't want to remove liters of solvent under vacuum.

 

[PlanckB1]

Get reasonably pure LA is a pain in the ass, nearly all the hydrolysis lead to brown/black product which as to be purified.
Even with good quality LA the coupling reaction mixture gets brown black and the work up is not as simple as it is stated (maybe if you start with 100% pure precursors, solvents degassed and professional equipment you have a small change of not happening, but for the home chemist dark solution has to be expected).
Purification of the product is no joke if you don't have access to column chromatography or if you don't want to remove liters of solvent under vacuum.

NicoinoThis has been my experience as well, repeated recrystallisations of the lysergic acid from hydrolysis resulting in a powder which becomes lighter brown each time but still not as light/pure as you would expect. Do you recommend column chromatography of the LA or just column chromatography of the final freebase LSD?

 

[Nicoino]

This has been my experience as well, repeated recrystallisations of the lysergic acid from hydrolysis resulting in a powder which becomes lighter brown each time but still not as light/pure as you would expect. Do you recommend column chromatography of the LA or just column chromatography of the final freebase LSD?

PlanckB1I don't think it's worth on the LA, probably with a good workup and enough experimentation it's not even need on the final product.
Big acid chemist like pichard used to synth kilos every month, and I really doubt they were able to chromatograph that amount of product, nearly impossible with a factory.

 

[dd^YrVmgVfy#8nL4GN^J]

@G.Patton @William Dampier , can sodium hydroxide or potassium hydroxide be used instead?

Is the ammonium hydroxide used to reach certain PH or does it donate an ion?

Does any vendor offer: "ammonium hydroxide (NH4OH) "?

 

[G.Patton]

@G.Patton @William Dampier , can sodium hydroxide or potassium hydroxide be used instead?

Is the ammonium hydroxide used to reach certain PH or does it donate an ion?

Does any vendor offer: "ammonium hydroxide (NH4OH) "?

dd^YrVmgVfy#8nL4GN^JIt's worth to use NH4OH, it's milder basifying agent. Of course it is widely sold.

Is the ammonium hydroxide used to reach certain PH or does it donate an ion?

pH changing means ions concentration changing in general. Don't understand what do u mean.

 

[nutella]

Hi @William Dampier thank you for the synthesis route.

I am not a expert, I have only experience on CBD isomerization to d8.
Now I'm trying to figure out whether it's possible for me to make LSD.

My current goals are:

1. Find detailed route from D-Lysergic Acid Methyl Ester
2. Obtain all reagents
3. Learning safe handling of the reagents
4. Learning Thin-layer chromatography
5. Learning Column (Flash) Chromatography
6. Make LSD
7. Recycling and safe disposal of reagents

I hope you can help me with my Questions:

• You write that we need 0.84 g Diethylamine (cas 109-89-7), is that correct?
• I ask because according to https://www.sigmaaldrich.com/ it is a liquid and I saw it from Chinese sellers sold in kg.
• Which TLC plates are best suited for this synthesis?
  • H type does not contain calcined gypsum binder or fluorescent agent.
  • G type does not contain fluorescent agent, contains calcined gypsum binder.
  • HF254 type contains fluorescent agent, does not contain calcined gypsum binder
  • GF254 type contains both calcined gypsum binder and fluorescent agent
• Can you help me with the route from D-Lysergic Acid Methyl Ester?

Thanks

 

[HerrHaber]

Hi @William Dampier thank you for the synthesis route.

I am not a expert, I have only experience on CBD isomerization to d8.
Now I'm trying to figure out whether it's possible for me to make LSD.

My current goals are:

1. Find detailed route from D-Lysergic Acid Methyl Ester
2. Obtain all reagents
3. Learning safe handling of the reagents
4. Learning Thin-layer chromatography
5. Learning Column (Flash) Chromatography
6. Make LSD
7. Recycling and safe disposal of reagents

I hope you can help me with my Questions:

• You write that we need 0.84 g Diethylamine (cas 109-89-7), is that correct?
• I ask because according to https://www.sigmaaldrich.com/ it is a liquid and I saw it from Chinese sellers sold in kg.
• Which TLC plates are best suited for this synthesis?
  • H type does not contain calcined gypsum binder or fluorescent agent.
  • G type does not contain fluorescent agent, contains calcined gypsum binder.
  • HF254 type contains fluorescent agent, does not contain calcined gypsum binder
  • GF254 type contains both calcined gypsum binder and fluorescent agent
• Can you help me with the route from D-Lysergic Acid Methyl Ester?

Thanks

nutellaIt so happens that diethylamine is not regulated in some countries and I have access to it, so subgram quantities can be thought of sendable especially in a protected form. Within this particular synthesis I think it can be eluted through GF254.

 

[nutella]

It so happens that diethylamine is not regulated in some countries and I have access to it, so subgram quantities can be thought of sendable especially in a protected form. Within this particular synthesis I think it can be eluted through GF254.

HerrHaberBuying water is not a problem, it just puzzles me that the quantity is not in ml but in g. It's a liquid

 

[nutella]

Buying water is not a problem, it just puzzles me that the quantity is not in ml but in g. It's a liquid

nutellaSorry i mean diethylamine

 

[HerrHaber]

Sorry i mean diethylamine

nutellaIn this very particular situation the liquid is weighed for precision... volumetrically you need a micropipette to get accurate quantities. Some times precision is decisive in synthesis, also methyl-diethylamine NMe(Et)2 needs to be precise. Large volumes are seldom weighed.... since volume is easier depending on viscosity and reactivity. Honey like stuff is clearly easyer to weigh and reactive liquids may be approached with syringe volume wise but sometimes if the quantity is small it is pipetted in a flask on a scale drop by drop to the needed mass. Under inert athmosphere is tricky and requires schlenk line and equipment ideally a glovebox (schlenk line and all the paraphrenalia like Argon and liquid nitrogen traps), glovebox I fantasized of building one (I actually built a working microscope when I was seven).

 

[verstappen]

What inert conditions are required for this reaction?

 

[S1NTH3T1C]

Reagents: View attachment 7892 ​

• Lysergic acid (cas 82-58-6)2.80 g;​
• Methylene chloride (DCM; CH2Cl2) 190 ml;​
• N,N-Diethylmethylamine (cas cas 616-39-7) 1.81 g;​
• PyBOP (cas 128625-52-5) 5.70 g;​
• Diethylamine (cas 109-89-7) 0.84 g;​
• Ammonium hydroxide (NH4OH) 100 ml 7.5 M;​
• Sodium bicarbonate (cold saturated aq solution) NaHCO3 40 ml;​
• Ethyl acetate (EtOAc) 60 ml;​
• Sodium sulphate (MgSO4) ~50 g;
• Deionized H2O ~200 ml;

Equipment and glassware:​

• Round bottom flask 250 mL;
• Retort stand and clamp for securing apparatus;
• Magnetic stirrer;
• Separatory funnel 500 mL (optional);
• Glass rod and spatula;
• Laboratory scale (0.1-100 g is suitable);
• Measuring cylinder 100 mL;
• Funnel;
• Filter paper;
• Rotovap machine (optional);
• Vacuum source;
• Buchner flask and funnel;
• Beakers 100 ml x2 and 250 ml x2;

View attachment 717​

Lysergic acid 2.80 g is added to a methylene chloride (DCM; CH2Cl2) 100 ml with a constant stirring. N,N-Diethylmethylamine 1.81 g is added to the reaction mixture and the solution is stirred for 5 min. Then PyBOP 5.70 g is added, and the solution is stirred for an additional 5 min. Then, diethylamine 0.84 g is added and the reaction is stirred at room temperature for 60 min.

The reaction mixture is quenched with concentrated ammonium hydroxide (NH4OH) 100 ml 7.5 M. Layers are separated, the aqueous phase is extracted with 3x30 ml DCM. Organic layers are combined and evaporated in a rotovap machine at 35 °C under high vacuum.

The residue is dissolved in sodium bicarbonate (cold saturated aq solution) NaHCO3 40 ml and extracted with 3x20 ml EtOAc. Organic layers are combined and washed with deionized H2O, brine, and dried over MgSO4. Solution is filtered and evaporated in a rotovap machine at 40 °C under vacuum to a constant weight. A yield is 3.13 g before chromatograp. ​

William DampierIs there an alternative to using a rotovap machine?

 

[WillD]

Is there an alternative to using a rotovap machine?

S1NTH3T1C

Vacuum Distillation Set

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Settings of this type as an example. With a vacuum pump.

 

[RaraOppapapOma]

Imagine doing that in a fucking school bus that would be amazing!

 

[mountainmomma]

Hey guys after the hydrolysis of the la how do you Purify the la. only method i can find you need amonia with anhydrous ethanol. I cant get these reagents. Is there another way to Purify the la for the pybop rxn

 

[CryoThio]

My question is if another amine can replace the diethylmethylamine? Say diisopropylamine, or diisopropylethylamine? Anything?