D-LAME to Lysergic Acid?

[PlanckB1]

Hi all,

If someone were to wish to convert D-LAME (D-lysergic acid methyl ester) into the carboxylic acid form (lysergic acid), would it be standard to do this via hydrolysis of the ester with something like NaOH/KOH then neutralize it with HCL?

What temperature could this reaction be done at? I don't have access to a rotovap and wish to keep the temperature as low as reasonably possible to not degrade the lysergic acid.

Thank you for all the help.

 

[HerrHaber]

Very good question, alkaline hydrolysis is bound to racemize the product which you most probably don’t want. I imagine that the new method with carboxyl activator can be worked in such way that hydrolysis occurs in tandem with the amidation thus leaving the substrate chirality the way it is. The way I got this largely documented also had me read a statement according to which synthesis in ethyl acetate can facilitate the yield of a resulting amide by having the ethyl ester formed in stiu from the acid. Now I can’t remember if this was commented regarding lysergic acid or just SPPS (solid phase peptide synthesis).

 

[PlanckB1]

Very good question, alkaline hydrolysis is bound to racemize the product which you most probably don’t want. I imagine that the new method with carboxyl activator can be worked in such way that hydrolysis occurs in tandem with the amidation thus leaving the substrate chirality the way it is. The way I got this largely documented also had me read a statement according to which synthesis in ethyl acetate can facilitate the yield of a resulting amide by having the ethyl ester formed in stiu from the acid. Now I can’t remember if this was commented regarding lysergic acid or just SPPS (solid phase peptide synthesis).

HerrHaberThank you very much for the help

I realise now that I definitely should have been referring to acidic hydrolysis so thanks for pointing out that alkaline hydrolysis would racemize the product. Is it possible for D-LAME to hydrolyze to the carboxylic acid form without the presence of the carboxyl activator? Or will it form LSA (the amide) without the activator? Sorry if I misinterpreted your reply but would you still use ethyl acetate as the solvent if trying to form lysergic acid? Thank you for all the help again, apologies if I say things which don't make a lot of sense, still trying to improve my understanding.

 

[CryoThio]

Very good question, alkaline hydrolysis is bound to racemize the product which you most probably don’t want. I imagine that the new method with carboxyl activator can be worked in such way that hydrolysis occurs in tandem with the amidation thus leaving the substrate chirality the way it is. The way I got this largely documented also had me read a statement according to which synthesis in ethyl acetate can facilitate the yield of a resulting amide by having the ethyl ester formed in stiu from the acid. Now I can’t remember if this was commented regarding lysergic acid or just SPPS (solid phase peptide synthesis).

HerrHaberJust to make sure I understand, as I'm not very educated in chemistry, are you saying LSMeEster could be directly reacted with PyBOP without hydrolysis, and still achieve LSD?

 

[HerrHaber]

First of all is somewhat clear that D-LAME is the starting material and we aim to preserve chirality at all costs, peptide chemistry is pretty much like this but has also need for a great yield since it’s repetitive, and cumulated losses make the product expensive. We can assume a slightly more modest yield in favor of product purity. You should note that the hydrolysis in a classical sense is a separate procedure and basic hydrolysis is employed. I never heard of acid conditions on this famously sensitive substrate where I imagine would start acting naughty with the product, and since acid would be catalyst, the product will start decomposing as it forms. Let’s just say inapplicable, the activator from which I choose PyBOP May react with the carboxyl to make it reactive towards nucleophyles such as amines in presence of another tertiary amine (MeEt2N) that needs to catch the resulting proton. Wether AcOEt is compatible or not must be tried but conditions for this activator are really mild. I find myself in a funny position to not be prompt with the most basic of the reactions... if ergot extract was the starting material alkaline hydrolysis with KOH was the way and reusing the resulting iso by racemization. When pure D ester is the start I am sure direct procedures ending with secondary amide have been developed. Maybe with some kind of catalytic bump that is needed to hydrolize part of the ester, so ethyl acetate would also be subjectable and this can be both good and bad news.

 

[CaptainSandoz]

Hi all,

If someone were to wish to convert D-LAME (D-lysergic acid methyl ester) into the carboxylic acid form (lysergic acid), would it be standard to do this via hydrolysis of the ester with something like NaOH/KOH then neutralize it with HCL?

What temperature could this reaction be done at? I don't have access to a rotovap and wish to keep the temperature as low as reasonably possible to not degrade the lysergic acid.

Thank you for all the help.

PlanckB1Hello I performed the synth many times. You can run it in alkaline water under inert atmosphere at 50°C until total dissolution then keep stirring several hours and acidify the mixture to précipite out the hydrate form of your amino acid.

 

[HerrHaber]

Hello I performed the synth many times. You can run it in alkaline water under inert atmosphere at 50°C until total dissolution then keep stirring several hours and acidify the mixture to précipite out the hydrate form of your amino acid.

CaptainSandozIt’s fenomenal news given the circumstance can you give the enantiomeric ratio and yield, perhaps concentration of agents and substrate with the volume of solvent. Or at least a beilstein style short description of procedure that I can develop on with the least amount of R&D time and losses. Hydrolysis with no chiral effect is what we all wish to have a starting procedure to work with. Please help the community with an attempt of a descriptive procedure. If it helps me I intend to give most for free so there be many more who will thank you and have the life changing trip.

 

[PsychedelicDog]

Hello I performed the synth many times. You can run it in alkaline water under inert atmosphere at 50°C until total dissolution then keep stirring several hours and acidify the mixture to précipite out the hydrate form of your amino acid.

CaptainSandozI’m also interested in a descriptive procedure. I’d say hardest part in making lsd is getting Lysergic acid, d-lame has a lot of potential as it is widely available.

 

[Inferior]

Sorry guys stupid question

D-Lysergic Acid Methyl Ester CAS 4579-64-0​

Is psicoactive? Thanks

 

[CryoThio]

Sorry guys stupid question

D-Lysergic Acid Methyl Ester CAS 4579-64-0​

Is psicoactive? Thanks

InferiorIt is not

 

[Rabidreject]

One day…one day….probably by the time that d-lame has been banned and they’ve found another way around it but at some stage in my life, I WILL get there…still there’s a whole book of phenethylamines, I should probably start with!