|LSD synthesis by Will L. Garbrecht|
From:Journal of Organic Chemistry vol.24,368-372('59)
The preparqation of L.A. amides. General procedure. A soln. of 7.15 g. of + Lysergic acid monohydrate (25.0 mmol.) and 1.06 g. of lithium hydroxide hydrate (25. mmol.) in 200 ml. of methanol was prepared. The solvent was distilled on the steam bath under reduced pressure. The residue of glass-like lithium lysergate was dissolved in 400 ml. of anhydrous dimethylformamide. About 200 ml. of DMF was distilled at 15 mm. pressure through a 12-inch helices-packed colum. The resulting anhydrous soln. of lithium lysergate in DMF was cooled to 0 degrees and, with stirring, treated rapidly with 50.0 ml. of SO3-DMF soln. (1.0 molar. The mixture was stirred in the cold for 1 min. and then 125.0 mmol. diethylamine was added. The stirring and cooling were continued for 10 min. longer when 400 ml. of water was added to decompose the reation complex. After mixing throughly, 200 ml. of saturated aqueous saline soln. was added. The amide product was then isolated by repeated extraction with 500 ml. portions of ethylene dichloride. Tests with Van Urk reagent were used to indicate completeness of extraction.
The combined extract was dried and then cocentrated to a sirup under reduced pressure. It was usually good practice to avoid heating the extract or the sirup during the concentration.
The LSD was ordinarly isolated in a crystalline form from the sirup as a salt (tartrate), which usually crystallized readily from methanol-ether solvent mixtures. Occasionally, the product could be isolated crystalline as the free base. Sometimes it was necessary to resort to chromatography. See Hofmann's procedure for chromatography.
Preparation of sulfur trioxide-DMF complex (SO3-DMF) is given in this paper also.
Garbrecht's Classic LSD Synthesis
(Rated as: excellent)
Synthesis of Amides of Lysergic Acid
William L. Garbrecht
J. Org. Chem. 24, 368-372 (1958) (../rhodium/pdf /lsd.garbrech
Although interest in the chemistry and pharmacology of lysergic acid derivatives has remained high for many years, until recently only one useful method for converting lysergic acid into its amide derivatives has been recorded. This method as described by A. Stoll consists of cleaving ergot alkaloids with hydrazine. The resulting lysergic acid hydrazide on treatment with nitrous acid is converted into the azide which may be used to prepare the desired amide by acylation of an appropriate amine.
Also, some further info on this synth can be found in ../rhodium/chemistry /psyched