Methergine,Sandoz,US,1948
To a freshly prepared solution of 2 parts of d-isolysergic acid azide in 300 parts of either is added an ethereal solution of 2 parts of d-2-aminobutanol-1 and the mixture is left to stand at room temperature during 12 hours. The yellowish clear solution is then washed several times with some water, dried over sodium sulfate and the ether evaporated in vacuo. The crystallized residue is treated with a small quantity of acetone and filtered. Yield: 2.2 parts of d-isolysergic acid-d-1-hydroxybutylamide-2. On recrystallization from
some hot methanol the new compound is obtained in form of beautiful
polygonal crystals that melt with some decomposition at 192° to 194°C
(corr.).
1 part of the iso-compound is then dissolved in 10 parts of absolute ethanol
and an alcoholic potassium hydroxide solution is added thereto. The mixture is
left to stand at room temperature during 45 minutes. After this time
equilibrium is reached between lysergic acid and the isolysergic acid forms,
which can be checked by determination of the constancy of the optical
rotation of the solution. When this point is reached, potassium hydroxide is
transformed into potassium carbonate by bubbling through the solution a
stream of carbon dioxide; the thick crystal paste of potassium carbonate is
then diluted with 50 parts of ether, filtered and washed again with 50 parts of
ether.
The alcoholic ethereal filtrate is then dried over calcined potassium carbonate
and the solution evaporated, whereby 0.9 to 1 part of a mixture of d-lysergic
acid-d-1-hydroxybutylamide-2 and of d-isolysergic acid-d-1-
hydroxybutylamide-2 is obtained. In order to separate the isomers, the
residue is dissolved in 15 parts of hot chloroform and filtered from the small
quantity of inorganic salt, whereby on cooling down, the difficultly soluble
chloroform compound of d-lysergic acid-d-1-hydroxybutylamide-2 crystallizes
out. Yield: 0.4 part. This compound can be recrystallized from hot benzene,
whereby crystals melting with some decomposition at 172°C (corr.) are
obtained. It may then be reacted with maleic acid to give the maleate.
