Dried crude product of the partial acetylation of digoxin (42 g) prepared from
digitalis - is dissolved under reflux in acetone (480 ml) and n-hexane (2400
ml) is added to the solution with stirring. Fine crystals, which begin to
separate immediately, are left at room temperature for 5 hours, then they are
filtered with suction, washed with n-hexane and dried in vacuum at 40°C,
yielding 32 g of crude β-acetyldigoxin (product 1). Product 1 (31 g) is
dissolved under reflux in chloroform (500 ml) and toluene (2500 ml) is added
thereto with stirring. The crystals, which separate after standing for 6 hours at
room temperature, are filtered, washed with toluene and ether and dried in
vacuum yielding 29 g of β-acetyldigoxin (product 2). MP: 249°-251°C.
The filtrate, which results from the separation of product 1, is evaparated to
dryness in vacuum. The residue, which mainly contains unreacted digoxin, is
purified by recrystallization from pyridine/ether/water (3.5:5:40) and
repeatedly acetylated. It can then be recycled to produce more β-
acetyldigoxin. The filtrate resulting from the separation of product 2 is
evaporated to dryness. The resulting residue contains the di- and polyacetyl
derivatives of digoxin, which are deacetylated to digoxin in a known manner and later is returned to a further acetylation process and can then be recycled
to produce more β-acetyldigoxin.
Beta-Acetyldigoxin may be prepared from digoxin, acetic acid and
dicyclohexylcarbodiimide using the last one as a condensing agent.
