WO2008106900A8 - Method of manufacturing (3r, 4s) -1- (4-fluorophenyl) -3- [ (3s) -3- (4 -fluorophenyl) -3-hydroxypropyl) ] -4- (4-hyd roxyphenyl) -2-azetidinone - Google Patents

Method of manufacturing (3r, 4s) -1- (4-fluorophenyl) -3- [ (3s) -3- (4 -fluorophenyl) -3-hydroxypropyl) ] -4- (4-hyd roxyphenyl) -2-azetidinone

Info

Publication number
WO2008106900A8
WO2008106900A8 PCT/CZ2008/000023 CZ2008000023W WO2008106900A8 WO 2008106900 A8 WO2008106900 A8 WO 2008106900A8 CZ 2008000023 W CZ2008000023 W CZ 2008000023W WO 2008106900 A8 WO2008106900 A8 WO 2008106900A8
Authority
WO
WIPO (PCT)
Prior art keywords
fluorophenyl
general formula
azetidinone
hydroxypropyl
manufacturing
Prior art date
Application number
PCT/CZ2008/000023
Other languages
French (fr)
Other versions
WO2008106900A1 (en
Inventor
Marketa Slavikova
Petr Velisek
Iva Obadalova
Josef Hajicek
Original Assignee
Zentiva As
Marketa Slavikova
Petr Velisek
Iva Obadalova
Josef Hajicek
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zentiva As, Marketa Slavikova, Petr Velisek, Iva Obadalova, Josef Hajicek filed Critical Zentiva As
Publication of WO2008106900A1 publication Critical patent/WO2008106900A1/en
Publication of WO2008106900A8 publication Critical patent/WO2008106900A8/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

A method of manufacturing (3R,4S)-l-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3- hydroxypropyl)]-4-(4-hydroxyphenyl)-2-azetidinone (Ezetimibe) of formula I, starting from the optically active (S)-N-acyl-oxazolidide of formula II, which is reacted with an alkyleneglycol of general formula III, (stage 1), and the obtained acetal-oxazolidide of general formula IV, is subjected to reaction with a silyl-imine of general formula V the produced amino-oxazolidide of general formula VI, (stage 3), and the obtained silylated azetidinone of general formula VII, is desilylated (stage 4), and the ketal of general formula VIII produced this way, is deketalized formula IX is finally reduced.
PCT/CZ2008/000023 2007-03-02 2008-03-03 Method of manufacturing (3r, 4s) -1- (4-fluorophenyl) -3- [ (3s) -3- (4 -fluorophenyl) -3-hydroxypropyl) ] -4- (4-hyd roxyphenyl) -2-azetidinone WO2008106900A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZPV-2007-170 2007-03-02
CZ20070170A CZ302395B6 (en) 2007-03-02 2007-03-02 Process for preparing (3R,4S)-l-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3- hydroxypropyl)]-4-(4-hydroxyphenyl)-2-azetidinone

Publications (2)

Publication Number Publication Date
WO2008106900A1 WO2008106900A1 (en) 2008-09-12
WO2008106900A8 true WO2008106900A8 (en) 2008-11-06

Family

ID=39432207

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2008/000023 WO2008106900A1 (en) 2007-03-02 2008-03-03 Method of manufacturing (3r, 4s) -1- (4-fluorophenyl) -3- [ (3s) -3- (4 -fluorophenyl) -3-hydroxypropyl) ] -4- (4-hyd roxyphenyl) -2-azetidinone

Country Status (2)

Country Link
CZ (1) CZ302395B6 (en)
WO (1) WO2008106900A1 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU0501164D0 (en) * 2005-12-20 2006-02-28 Richter Gedeon Vegyeszet New industrial process for the production of ezetimibe
WO2010113175A2 (en) 2009-04-01 2010-10-07 Matrix Laboratories Ltd Enzymatic process for the preparation of (s)-5-(4-fluoro-phenyl)-5-hydroxy- 1morpholin-4-yl-pentan-1-one, an intermediate of ezetimibe and further conversion to ezetimibe
ES2372460B1 (en) 2010-07-09 2012-11-16 Moehs Ibérica S.L. NEW METHOD FOR THE PREPARATION OF EZETIMIBA.
WO2012076030A1 (en) * 2010-12-10 2012-06-14 Pharmathen S.A. Process for the preparation of intermediate compounds useful in the preparation of ezetimibe
CN102731489B (en) * 2011-04-11 2016-10-26 天津药物研究院有限公司 A kind of preparation method of key ezetimibe intermediate
CN103159751A (en) * 2011-12-13 2013-06-19 重庆华邦胜凯制药有限公司 A preparation method for the derivates of phenylpyruvic acid amide ketals
CN104003921A (en) * 2014-05-06 2014-08-27 南通常佑药业科技有限公司 Preparation method of ezetimibe intermediate
CN104513187B (en) * 2015-01-09 2017-05-31 安润医药科技（苏州）有限公司 The synthetic method of Ezetimibe and its intermediate
CN107118144B (en) * 2016-02-24 2020-04-10 上海医药工业研究院 Reduction preparation process of ezetimibe and intermediate thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5886171A (en) * 1996-05-31 1999-03-23 Schering Corporation 3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones
DE102004025072A1 (en) * 2004-05-21 2005-12-15 Sanofi-Aventis Deutschland Gmbh Process for the preparation of diphenyl-azetidinone derivatives
CA2613239A1 (en) * 2005-06-22 2006-12-28 Manne Satyanarayana Reddy Improved process for the preparation of ezetimibe
HU0501164D0 (en) * 2005-12-20 2006-02-28 Richter Gedeon Vegyeszet New industrial process for the production of ezetimibe
US20090227786A1 (en) * 2005-12-22 2009-09-10 Ana Gavalda I Escude Processes for preparing intermediate compounds useful for the preparation of ezetimibe

Also Published As

Publication number Publication date
CZ302395B6 (en) 2011-04-27
WO2008106900A1 (en) 2008-09-12
CZ2007170A3 (en) 2008-10-22

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