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Title:
PROCESS FOR THE PREPARATION OF 4-(4-AMINOPHENYL)MORPHOLIN-3-ONE
Document Type and Number:
WIPO Patent Application WO/2019/138362
Kind Code:
A1
Abstract:
The field of this invention relates to a novel process, suitable for industrial scale manufacture, for the preparation of 4-(4-aminophenyl)morpholin-3-one of Formula (I), the key intermediate of rivaroxaban according to the scheme. In the process 2-(2-chloroethoxy)ethanol of Formula (XI) is oxidized to 2-(2-chloroethoxy)- acetic acid with aqueous sodium- or calcium-hypochlorite and a catalyst. The 2-(2~ chloroethoxy)acetic acid of Formula (X) is reacted with 4-nitro-aniline of Formula (VII) with phenylboronic acid catalyst. Then the 2-(2-chloroetoxy)-N-(4-nitrophenyl)acetamide of Formula (IX) is transformed to 4-(4-nitrophenyl)morpholin-3-one of Formula (IV) in a „one- pot" procedure. The 4-(4-nitrophenyl)morpholin-3-one of Formula (IV) is hydrogenated to get 4-(4-aminophenyl)morpholin-3-one of Formula (I).

Inventors:
SZABÓ TAMÁS (HU)
NEU JÓZSEF (HU)
GARADNAY SÁNDOR (HU)
Application Number:
IB2019/050213
Publication Date:
July 18, 2019
Filing Date:
January 11, 2019
Export Citation:
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Assignee:
RICHTER GEDEON NYRT (HU)
International Classes:
C07D265/32; C07C51/16; C07C231/02
Domestic Patent References:
WO2005026135A12005-03-24
WO2008075152A12008-06-26
Foreign References:
CN102464580A2012-05-23
CN104098525A2014-10-15
US20030153610A12003-08-14
EP164O373A1
Other References:
ANIL C MALI ET AL: "Facile approach for the synthesis of rivaroxaban using alternate synthon: reaction, crystallization and isolation in single pot to achieve desired yield, quality and crystal form", SUSTAINABLE CHEMICAL PROCESSES, vol. 48, no. 1, 13 July 2015 (2015-07-13), pages 5900, XP055230109, DOI: 10.1186/s40508-015-0036-3
MEDERSKI ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, 2004, pages 58 17 - 5822
MALI ET AL., SUSTAIN CHEM. PROCESS, vol. 3, 2015, pages 11
"Bioorganic & Medicinal Chemistry Letters", vol. 14, 2004, pages: 5817 - 5822
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