A suspension of 1.34g (5mmol) anhydrous D-Lysergic Acid in 80ml DMF was mixed at 20°C with a solution of 0.89g (5.5mmol) N,N'-Carbonyldiimidazole in 25ml DMF and the reaction mixture was then stirred for 30 min at 20°C in the dark. The clear solution was then mixed with a solution of 0.40g (5.5mmol) Diethylamine in 5ml DMF, and the mixture allowed to stand for 2h at 20°C followed by 20h at 5°C. The resulting amber solution was freed from DMF by evaporation at 50-60°C under aspirator vacuum, the residue dissolved in 250mL 2% aqueous tartaric acid and the solution washed with diethyl ether. To the aqueous phase was added a small amount of Ostacol (activated carbon), the solution filtered with suction and basified to pH 8 with aqueous ammonium hydroxide. The liberated freebase was extracted with a 9:1 ether/ethanol mixture, and after separation and drying of the organic phase, the solvent was evaporated in vacuo to give 2.3g of crude product, which consisted of 57 weight% of the diethylamides of D-Lysergic acid (I) and D-Isolysergic acid (II) (81% yield calculated on the starting acid) and the rest being chiefly Imidazole. According to qualitative TLC analysis the crude product contained only the amides (I) and (II) as well as traces of D-Lysergic acid and a decomposition product.
The crude base mixture was dissolved in 10ml 99:1 benzene/acetone and chromatographed on 50g alumina (activity III-IV) using the same solvent mixture as eluent to separate the different fractions. From the first fractions, 0.93g very pure D-Lysergic acid Diethylamide, [a]20/D+26° (c=0.30; Pyridine). Following recrystallization from methanol, the physical properties of the neutral D-Lysergic Acid Diethylamide L-Tartrate was found to be identical to an authentic sample; mp 198-200°C, [a]20/D 31° (c=0.92; Water). Upon drying in a vacuum dessiccator at 100°C/0.2mmHg the substance lost 5.02% of its weight. For (C20H25N3O)2.C4H6O6 (796.9 g/mol) calculated: 10.55% N; found: 10,48% N.
Reference: Svensk Farmaceutisk Tidskrift Vol. 75, pp. 933-40 (1971)