New high yield d-LSD synthesis

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AMARUK
(Stranger)
07-16-04 05:49
No 519740
Re:New high yield d-LSD synthesis


I have found new method of preparing lysergic acid amides with yield of 80%. In this method isomerisation of d-lysergic acid amide to d-iso-lysergic acid amide never occurs. Czech Patent Aplication 287 047 describe this new superior method of preparing only d-lysergic acid amides as end product by treating d-lysergic acid in a solvent(i.e. DMF, ethyl acetate, toluene, acetone, THF, dioxan) with solution
(in one of above mentioned solvent) of propane phosphoric acid anhydride(coupling agent) of formula:

   I    O    I
   I    II I
   ---I----P--O----I---
   I    I    I
   I    C3H7    I
   I    I   m>3

with the aid of base(triethylamine, pirydine, N-ethylpiperidine, NaOH, KOH, anhydrous Na2CO3 or K2CO3) in temp. from -10 C deg to +130 C deg.

Example 1. d-lysergic acid S-(+)-1-buthanolamide (methylergometrine)

   To a solution of 1.3 g of   d-lysergic acid in 50 ml of dimethyl formamide (DMF) was added   0.8 ml of S-(+)-1-buthanolamine and mixture was cooled to +5 C deg and next 1,6 ml of triethylamine was added and stirred for 25 minutes in temp. of +5 C deg. The reaction was then treated with 5,3 ml of 50%propane phosphoric acid anhydride solution in DMF and stirred at room temperature for 1 hour. To the reaction mixture was then added 0,4 g of activated carbon an stired for 15 minutes and insoluble material was removed by filtration . To the reaction mixture was then added 50 ml of water and extracted with   50 ml of methylene chloride. The organic layer was separated and washed with two portion of 50 ml water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was chromatographed on 50 g of silica gel using 3% methanol in methylene chloride to yield 1.3 g (80%) of d-lysergic acid S-(+)-1-buthanolamide.

Example 6. N-[3-(dimethylamino)propyl]-6-methyl-ergolin-8b-carboxamid

   To a solution of 1.3 g of   d-dihydrolysergic acid in 120 ml of ethyl acetate was added   2.0 ml of N,N-dimethyl-trimethylendiamine and mixture was cooled to +5 C deg and next 4,0 ml of triethylamine was added and stirred for 25 minutes in temp. of +5 C deg. The reaction was then treated with 8,0 ml of 50%propane phosphoric acid anhydride solution in DMF and stirred at room temperature for 1 hour. To the reaction mixture was then added 0,4 g of activated carbon an stired fo 15 minutes and insoluble material was removed by filtration . To the reaction mixture was then extracted with   50 ml of saturated solution of NaHCO3. The organic layer was separated and concentrated under reduced pressure. Yield 1.58 g (92,9%).

   This Patent(CZ287047) gives no information in which form lysergic acid was used(monohydrate or dry?). Could somebee find some articels described similar peptide condensation using propane phosphoric acid anhydride of above formula(reaction conditions, purity of reagents, water content in solvents, how dry must be carboxylic acid?).
   Where to buy propane phosphoric acid anhydride or how it prepare?
   What CAS Number have propane phosphoric acid anhydride?

Thanks for your HELP!!!   WILK 06:44 2004-04-05

Lilienthal
(Moderator)
07-16-04 07:05
No 519743
Re:CZ287047 (please use the patent markup!


Patent CZ287047 (please use the patent markup: ([patent]CZ287047[/patent]!)

hest
(Hive Adickt)
07-16-04 08:54
No 519754
Re:Propylphosphonsaeureanhydrid made from the...

Propylphosphonsaeureanhydrid made from the acid chloride.
Newer heard about it before, Aldrich don't sell it.
Butt if siomeone would translate the interesting part's (p 6 and 7) of the patent ill look into it

longimanus
(Newbee)
07-16-04 11:29
No 519766
Re:Can someone, please, translate the ...

Can someone, please, translate the "PATENTOV… N¡ROKY" part, I`m not very good at Czech. It`s interesting that only the preparation of monosubstituted lysergamides was described. And the mentioned above part would tell us if the method is appropriate for LSD.

UHH, and since 5gr propylphosphonic acid (not even the anhydride) cost ~$190 it won`t be the cheapest synthesis!