Process for the preparation of iloprost

A process of iloprost of formula I

• comprising that
• a.) the Corey lactone of formula II
• is selectively alkylated with dimethyl methylphosphonate in the presence of lithium dialkylamide,
• b.) the ring of the resulting lactol of formula III
• is opened with pyridinium acetate in weak acidic medium, then the obtained secondary hydroxyl group is oxidized with pyridinium dichromate,
• c.) the resulting compound of formula IV
• is reacted with potassium carbonate in the presence of 18-crown-6 reagent,
• d.) the thus obtained compound of formula V
• is reduced,
• e.) the resulting compound of formula VI
• is reacted with carboxybutyltriphenylphosphonium bromide in the presence of potassium tertiary-butylate,
• f.) the TBDMS protecting group of the resulting E- and Z-isomers of formula VII
• is removed, the isomers are separated by gravitational chromatography, if desired the Z-isomer (VIIIz) is isomerized into the E-isomer,
• g.) the resulting compound of formula VIII
• is esterified,
• h.) the resulting compound of formula IX
• is oxidized,
• i.) the resulting compound of formula X
• is transformed in HWE reaction in the presence of solid potassium hydroxide into the compound of formula XI,
• j.) the oxo group of the resulting compound of formula XI
• is reduced with DIBAL-F,
• k.) the tetrahydropyranyl protecting group of the thus obtained compound of formula XII
• is removed and the compound is purified by gravitational column chromatography, if desired further purified by preparative HPLC,
• l.) the ester group of the resulting compound of formula XIII
• is removed and the obtained compound of formula I is purified.