CA2255662A1 - 3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones - Google Patents

3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones

Info

Publication number
CA2255662A1
CA2255662A1 CA002255662A CA2255662A CA2255662A1 CA 2255662 A1 CA2255662 A1 CA 2255662A1 CA 002255662 A CA002255662 A CA 002255662A CA 2255662 A CA2255662 A CA 2255662A CA 2255662 A1 CA2255662 A1 CA 2255662A1
Authority
CA
Canada
Prior art keywords
azetidinones
enantioselective synthesis
lactone based
hydroxy gamma
lactone
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA002255662A
Other languages
French (fr)
Other versions
CA2255662C (en
Inventor
Guang-Zhong Wu
Xing Chen
Yee-Shing Wong
Doris P. Schumacher
Martin Steinman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme LLC
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2255662A1 publication Critical patent/CA2255662A1/en
Application granted granted Critical
Publication of CA2255662C publication Critical patent/CA2255662C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

Abstract

The invention relates to a process for producing a compound of formula (I) wherein R1, R2 and R3 are as defined in the specification, which comprises reacting a lactone with an imine to obtain a chiral diol of formula (IV) oxidizing the diol, condensing the resultant aldehyde with an enolether, hydrogenating the product, and chirally catalytically reducing the resultant ketone.
CA002255662A 1996-05-31 1997-05-28 3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones Expired - Fee Related CA2255662C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/655,785 US5739321A (en) 1996-05-31 1996-05-31 3-hydroxy γ-lactone based enantionselective synthesis of azetidinones
US08/655,785 1996-05-31
PCT/US1997/009666 WO1997045406A1 (en) 1996-05-31 1997-05-28 3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones

Publications (2)

Publication Number Publication Date
CA2255662A1 true CA2255662A1 (en) 1997-12-04
CA2255662C CA2255662C (en) 2005-11-08

Family

ID=24630339

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002255662A Expired - Fee Related CA2255662C (en) 1996-05-31 1997-05-28 3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones

Country Status (14)

Country Link
US (1) US5739321A (en)
EP (1) EP0906278B1 (en)
JP (1) JP3155759B2 (en)
AR (1) AR007314A1 (en)
AT (1) ATE226191T1 (en)
AU (1) AU3299497A (en)
CA (1) CA2255662C (en)
CO (1) CO4770966A1 (en)
DE (1) DE69716426T2 (en)
DK (1) DK0906278T3 (en)
ES (1) ES2185026T3 (en)
PT (1) PT906278E (en)
WO (1) WO1997045406A1 (en)
ZA (1) ZA974678B (en)

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DE60206365T2 (en) 2001-03-28 2006-07-06 Schering Corporation, Kenilworth PROCESS FOR THE ENANTIOSELECTIVE SYNTHESIS OF AZETIDINONE INTERMEDIATE PRODUCTS
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US7176194B2 (en) 2002-06-19 2007-02-13 Sanofi-Aventis Deutschland Gmbh Ring-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use
US7176193B2 (en) 2002-06-19 2007-02-13 Sanofi-Aventis Deutschland Gmbh Acid-group-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use
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US7135556B2 (en) * 2002-07-19 2006-11-14 Schering Corporation NPC1L1 (NPC3) and methods of use thereof
US7208486B2 (en) * 2003-03-07 2007-04-24 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7459442B2 (en) * 2003-03-07 2008-12-02 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7235543B2 (en) * 2003-03-07 2007-06-26 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
AR041089A1 (en) 2003-05-15 2005-05-04 Merck & Co Inc PROCEDURE AND PHARMACEUTICAL COMPOSITIONS TO TREAT ATEROSCLEROSIS, DYSLIPIDEMIAS AND RELATED AFFECTIONS
WO2005009955A1 (en) * 2003-07-31 2005-02-03 Hetero Drugs Limited Ezetimibe polymorphs
US7067675B2 (en) 2003-11-24 2006-06-27 Hetero Drugs Limited Process for ezetimibe intermediate
GB0329778D0 (en) * 2003-12-23 2004-01-28 Astrazeneca Ab Chemical compounds
ATE485267T1 (en) * 2003-12-23 2010-11-15 Astrazeneca Ab DIPHENYLAZETIDINONE DERIVATIVES WITH CHOLESTERINE ABSORPTION INHIBITING EFFECT
EP1723414A4 (en) * 2004-01-16 2008-03-26 Merck & Co Inc Npc1l1 (npc3) and methods of identifying ligands thereof
US20060211752A1 (en) 2004-03-16 2006-09-21 Kohn Leonard D Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression
US20070244107A1 (en) * 2004-08-25 2007-10-18 Waters M Gerard Method of Treating Atherosclerosis, Dyslipidemias and Related Conditions
EP1817280A1 (en) * 2004-12-03 2007-08-15 Teva Pharmaceutical Industries Ltd. Ezetimibe polymorphs
US20060234996A1 (en) * 2005-04-14 2006-10-19 Itai Adin Novel crystalline form of ezetimibe and processes for the preparation thereof
KR20080021082A (en) * 2005-06-20 2008-03-06 쉐링 코포레이션 Piperidine derivatives useful as histamine h3 antagonists
SA06270191B1 (en) * 2005-06-22 2010-03-29 استرازينيكا ايه بي Novel 2-Azetidinone Derivatives as Cholesterol Absorption Inhibitors for the Treatment of Hyperlipidaemic Conditions
AR054482A1 (en) * 2005-06-22 2007-06-27 Astrazeneca Ab DERIVATIVES OF AZETIDINONE FOR THE TREATMENT OF HYPERLIPIDEMIAS
US20070049748A1 (en) * 2005-08-26 2007-03-01 Uppala Venkata Bhaskara R Preparation of ezetimibe
US20070259845A1 (en) * 2005-09-08 2007-11-08 Kansal Vinod K Processes for the preparation of (3R,4S)-4-((4-benzyloxy)phenyl)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-2-azetidinone, an intermediate for the synthesis of ezetimibe
US20080255084A1 (en) 2005-10-21 2008-10-16 Randy Lee Webb Combination of Organic Compounds
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
US7910698B2 (en) 2006-02-24 2011-03-22 Schering Corporation NPC1L1 orthologues
WO2007108007A1 (en) * 2006-03-23 2007-09-27 Unichem Laboratories Limited A process for the preparation of ezetimibe via a novel intermediate
AR060216A1 (en) * 2006-03-29 2008-06-04 Medichem Sa PROCESSES TO PREPARE EZETIMIBE AND USEFUL INTERMEDIATE COMPOUNDS FOR PREPARATION
TW200811098A (en) * 2006-04-27 2008-03-01 Astrazeneca Ab Chemical compounds
BRPI0706041A2 (en) * 2006-08-29 2011-03-22 Teva Pharmaceutichal Ind Ltd (3r, 4s) -4- (phenyl-4-hydroxy-protected) -1- (4-fluorophenyl) -3- [3- (4-fluorophenyl) -3-oxoprophyl] azetidine-2-one processes for purification
CA2661404A1 (en) * 2006-09-05 2008-03-13 Schering Corporation Pharmaceutical combinations for lipid management and in the treatment of atherosclerosis and hepatic steatosis
WO2008032338A2 (en) * 2006-09-11 2008-03-20 Manne Satyanarayana Reddy Improved process for the preparation of ezetimibe and its intermediates
JP2010509216A (en) * 2006-11-02 2010-03-25 メルク エンド カムパニー インコーポレーテッド Heterocyclyl-substituted antihypercholesterolemic compounds
US20090047716A1 (en) * 2007-06-07 2009-02-19 Nurit Perlman Reduction processes for the preparation of ezetimibe
US20080319221A1 (en) 2007-06-22 2008-12-25 Bernd Junker Esters of Pentahydroxyhexylcarbamoyl Alkanoic Acids
DE102007063671A1 (en) 2007-11-13 2009-06-25 Sanofi-Aventis Deutschland Gmbh New crystalline diphenylazetidinone hydrates, medicaments containing these compounds and their use
CZ305066B6 (en) * 2008-02-25 2015-04-22 Zentiva, K.S. Process for preparing (3R, 4S)-l-(4-fiuorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3- hydroxypropyl)]-4-(4-hydroxyphenyl)-2-azetidinone
EP2128133A1 (en) * 2008-05-26 2009-12-02 Lek Pharmaceuticals D.D. Ezetimibe process and composition
PL387331A1 (en) * 2009-02-24 2010-08-30 Instytut Chemii Organicznej Polskiej Akademii Nauk Method of manufacturing beta-lactam aldehyde compound, the intermediate compound, method of manufacturing the intermediate compound and application of the intermediate compound
US9388440B2 (en) 2009-04-01 2016-07-12 Mylan Laboratories Limited 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
EP2566497B1 (en) 2010-05-04 2015-07-29 Codexis, Inc. Biocatalysts for ezetimibe synthesis
ES2372460B1 (en) 2010-07-09 2012-11-16 Moehs Ibérica S.L. NEW METHOD FOR THE PREPARATION OF EZETIMIBA.
CN102477008B (en) * 2010-11-22 2014-05-21 沈阳药科大学 Method for synthesizing ezetimibe
WO2012076030A1 (en) * 2010-12-10 2012-06-14 Pharmathen S.A. Process for the preparation of intermediate compounds useful in the preparation of ezetimibe
WO2012155932A1 (en) 2011-05-17 2012-11-22 Pharmathen S.A. Improved process for the preparation of ezetimibe
PL231215B1 (en) 2011-06-15 2019-02-28 Inst Chemii Organicznej Polskiej Akademii Nauk Process for the preparation of substituted azetidinones and intermediates for the synthesis thereof
CN103086938A (en) * 2011-10-28 2013-05-08 沈阳药科大学 Ezetimibe synthesis method
CN102531986A (en) * 2012-02-23 2012-07-04 苏州朗科生物技术有限公司 Preparation method for ezetimibe
CN103570574B (en) 2012-07-20 2016-04-13 中国科学院上海有机化学研究所 Intermediate used in a kind of synthetic method of ezetimibe and the method
CN103044305A (en) * 2013-01-24 2013-04-17 上海现代制药股份有限公司 Preparation method of ezetimibe intermediate
WO2015039675A1 (en) 2013-09-23 2015-03-26 Pharmathen S.A. Novel process for the preparation of ezetimibe intermediates
CN103739537B (en) * 2013-12-24 2015-05-20 连云港恒运医药科技有限公司 New synthesis method of ezetimibe
CN104072398B (en) * 2014-07-03 2016-02-03 河南省科学院化学研究所有限公司 A kind of method of synthesizing Ezetimibe
JP2016145173A (en) * 2015-02-09 2016-08-12 株式会社トクヤマ Method for producing (3r,4s)-1-(4-fluorophenyl)-[3(s)-hydroxy-3-(4-fluorophenyl)propyl]-(4-hydroxyphenyl)-2-azetidinone
CN107098841A (en) * 2016-02-19 2017-08-29 常州方楠医药技术有限公司 Intermediate used in the preparation method and this method of a kind of Ezetimibe
CN107033051A (en) * 2017-06-08 2017-08-11 武汉励合生物医药科技有限公司 A kind of preparation method of ezetimibe

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* Cited by examiner, † Cited by third party
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US5631365A (en) * 1993-09-21 1997-05-20 Schering Corporation Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents
WO1997016424A1 (en) * 1995-11-02 1997-05-09 Schering Corporation Process for preparing 1-(4-fluorophenyl)-3(r)-(3(s)-hydroxy-3-([phenyl or 4-fluorophenyl])-propyl)-4(s)-(4-hydroxyphenyl)-2-azetidinone

Also Published As

Publication number Publication date
WO1997045406A1 (en) 1997-12-04
DE69716426T2 (en) 2003-08-14
ES2185026T3 (en) 2003-04-16
EP0906278A1 (en) 1999-04-07
ATE226191T1 (en) 2002-11-15
JP3155759B2 (en) 2001-04-16
PT906278E (en) 2003-01-31
EP0906278B1 (en) 2002-10-16
US5739321A (en) 1998-04-14
JPH11511754A (en) 1999-10-12
CA2255662C (en) 2005-11-08
DK0906278T3 (en) 2003-02-17
DE69716426D1 (en) 2002-11-21
AU3299497A (en) 1998-01-05
CO4770966A1 (en) 1999-04-30
AR007314A1 (en) 1999-10-27
ZA974678B (en) 1997-11-28

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