Abstract: The present invention relates to a process for the preparation of iloprost of formula I through new intermediates, isolation of iloprost of formula I in solid form, as well as preparation of the 16(S)-iloprost and 16(R)-iloprost isomers of formulae (S)-I and (R)-I and isolation of iloprost of formula I and 16(S)-iloprost of formula (S)-I in solid, crystalline form.
Type:
Grant
Filed:
October 25, 2022
Date of Patent:
April 16, 2024
Assignee:
EUROAPI HUNGARY LIMITED LIABILITY COMPANY
Inventors:
Imre Rozsumberszki, Zsuzsanna Kardos, Irén Hortobágyi, Tibor Szabó, Csaba Váradi, Tamás Bán
Abstract: The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing the 15-oxo group of the compound of formula 16-(R)-10, thereby obtaining a compound of formula 15-(R,S), 16-(R)-11, followed by removing the protecting group of the compound of formula 15-(R,S), 16-(R)-11, and isolating the compound of formula 1, and optionally, crystallizing the compound of formula 1. Optionally, the undesired isomer formed during fractional crystallization can be epimerized and further amount of the desired isomer can be recovered from the resulting mixture. The present invention also provides novel intermediates useful in the process. The invention further relates to a process for fractional crystallization of the compound of formula 16-(R,S)-10.
Type:
Application
Filed:
December 16, 2020
Publication date:
April 13, 2023
Applicant:
EUROAPI HUNGARY LIMITED LIABILITY COMPANY
Inventors:
Irén HORTOBÁGYI, Zsuzsanna KARDOS, Máriusz KERTÉSZ, István LÁSZLÓFI, ILDIKÓ MELEG, Judit PÓTI, Andrea SÁNTÁNÉ CSUTOR, László TAKÁCS