Preparation of d-Lysergic Acid Diethylamide

The above procedure yields about 1.5 g. of crystals which melt indefinitely with decomposition on a Fisher John block at about 195° C. 

From the crystallization mother liquors, after concentration, neutralization, and re-extraction with ethylene dichloride, there can be obtained about 

of amorphous d-isolysergic acid morpholide. This material can be isomerized to d-lysergic acid morpholide by the procedure disclosed by Smith and Timmis in J. Chem. Soc. 139,11,1168 (1936). 

About 1.64 g. of potassium d-lysergic acid hydrate are suspended in about 25 mL. of anhydrous hexane. To the suspension is added a solution of 0.8 g. of sulfur trioxide dissolved in 25 mL. of acetonitrile, the addition being carried out with the reagents maintained at about 5° C., and with sufficient stirring. To the mixture is added a solution of about 1.82 g. of diethylamine dissolved in 25 mL. of ether. 

After standing for about five minutes the solution is extracted about five times with 100 mL. portions of water. The aqueous extracts are combined and are saturated with sodium chloride. The saturated solution is extracted five times with 100 mL. portions of ethylene dichloride. The ethylene dichloride extracts are combined and are evaporated in vacuo leaving a residual syrup comprising, a mixture of the diethylamides of d-lysergic and d-isolysergic acids. 

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