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WO2004022564A3 - Alternative processes for the preparation of d- (+) -morphine, and d- (+) - morphine tartrate - Google Patents

Alternative processes for the preparation of d- (+) -morphine, and d- (+) - morphine tartrate Download PDF

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Publication number
WO2004022564A3
WO2004022564A3 PCT/GB2003/003805 GB0303805W WO2004022564A3 WO 2004022564 A3 WO2004022564 A3 WO 2004022564A3 GB 0303805 W GB0303805 W GB 0303805W WO 2004022564 A3 WO2004022564 A3 WO 2004022564A3
Authority
WO
WIPO (PCT)
Prior art keywords
morphine
converting
under conditions
conditions effective
dihydrosinomenine
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.)
Ceased
Application number
PCT/GB2003/003805
Other languages
French (fr)
Other versions
WO2004022564A2 (en
Inventor
John Whittall
Paul Mather
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.)
Stylacats Ltd
Original Assignee
Stylacats Ltd
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 Stylacats Ltd filed Critical Stylacats Ltd
Priority to AU2003263301A priority Critical patent/AU2003263301A1/en
Publication of WO2004022564A2 publication Critical patent/WO2004022564A2/en
Publication of WO2004022564A3 publication Critical patent/WO2004022564A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a process for the production of (+)-morphine from (-)-sinomenine comprising contacting (-)-sinomenine with H2/Pd/C under conditions effective for converting sinomenine to 7(S)-(+)-dihydrosinomenine or 7(R)-(+)-dihydrosinomenine or a mixture thereof; contacting the resulting 7(S)-(+)-dihydrosinomenine or 7(R)-(+)-dihydrosinomenine or a mixture thereof with polyphosphoric acid or Eatons reagent under conditions effective for converting 7(S)-(+)-dihydrosinomenine or 7(R)-(+)-dihydrosinomenine or a mixture thereof to (+)-dihydrocodeinone; contacting the resulting (+)-dihydrocodeinone either with (MeO)3CH followed by TsOH followed by NBA/MeOH under conditions effective for converting (+)-dihydrocodeinone to (+)-1,7-dibromodihydrocodeinone dimethylketal; contacting the resulting (+)-1,7-dibromodihydrocodeinone dimethylketal with t-butoxide followed by acid under conditions effective for converting (+)-1,7-dibromodihydrocodeinone dimethylketal to (+)-1-bromocodeinone; contacting the resulting (+)-1­bromocodeinone with LiAlH4 followed by BBr3 under conditions effective for converting (+)-1-bromocodeinone to (+)-morphine; or with o-iodoxybenzoic acid (IBX) and 4-methoxypyridine-N-oxide under conditions effective for converting (+)-dihydrocodeinone to (+)-codeinone; contacting the resulting (+)-codeinone with sodium borohydride followed by BBr3 under conditions effective for converting (+)-codeinone to (+)-morphine; and in either case recovering the resulting (+)-morphine as product. The invention also relates to novel compounds produced during the process.
PCT/GB2003/003805 2002-09-03 2003-09-03 Alternative processes for the preparation of d- (+) -morphine, and d- (+) - morphine tartrate Ceased WO2004022564A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003263301A AU2003263301A1 (en) 2002-09-03 2003-09-03 Alternative processes for the preparation of d- (+) -morphine, and d- (+) - morphine tartrate

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0220385A GB2392670A (en) 2002-09-03 2002-09-03 (+)-Morphine production
GB0220385.9 2002-09-03

Publications (2)

Publication Number Publication Date
WO2004022564A2 WO2004022564A2 (en) 2004-03-18
WO2004022564A3 true WO2004022564A3 (en) 2004-07-01

Family

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Family Applications (1)

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PCT/GB2003/003805 Ceased WO2004022564A2 (en) 2002-09-03 2003-09-03 Alternative processes for the preparation of d- (+) -morphine, and d- (+) - morphine tartrate

Country Status (3)

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AU (1) AU2003263301A1 (en)
GB (1) GB2392670A (en)
WO (1) WO2004022564A2 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2357216T3 (en) 2005-06-16 2011-04-20 Mallinckrodt, Inc. A SYNTHESIS ROUTE OF 14-HYDROXYL-OPIACES THROUGH 1-HALO-THEBAINE OR ANALOGS.
AU2008276385B2 (en) * 2007-07-17 2013-07-18 SpecGx LLC Preparation of N-alkylated opiates by reductive amination
US8252928B2 (en) 2008-09-16 2012-08-28 Mallinckrodt LLC. Processes for the synthesis of five and six membered heterocyclic rings
AU2009322622B2 (en) * 2008-12-02 2015-03-12 Mallinckrodt Llc Process for preparing hydrocodone using a super acid
US8946419B2 (en) 2009-02-23 2015-02-03 Mallinckrodt Llc (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
JP2012518652A (en) * 2009-02-23 2012-08-16 マリンクロッド インコーポレイテッド (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
EP2398806A1 (en) * 2009-02-23 2011-12-28 Mallinckrodt LLC (+)-morphinanium n-oxides and processes for their production
US10363251B2 (en) 2009-07-16 2019-07-30 Mallinckrodt Llc (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof
TR201809739T4 (en) * 2009-07-16 2018-07-23 Mallinckrodt Llc (+) - morphinans as toll-like receptor 9 antagonists and their therapeutic use.
ES2728701T3 (en) 2010-07-16 2019-10-28 Mallinckrodt Llc (+) - Morphinans as antagonists of the Toll-type receptor 9 and therapeutic applications thereof
CN104672142B (en) * 2015-02-13 2017-08-04 江苏大学 Preparation and medical application of binary structure sinomenine derivatives
CN109666030B (en) * 2018-11-19 2021-04-27 兰州大学 A method for catalyzing asymmetric synthesis of codeine and morphine
JP2023518875A (en) * 2020-03-24 2023-05-08 ユニバーシティ オブ パドヴァ Morphinan isomers and their structural modifications as NMDAR antagonists and neuroplastogens

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4025520A (en) * 1974-04-10 1977-05-24 Macfarlan Smith Limited Dehydrohalogenation of a 7-halodihydrocodeinone dialkyl ketal
WO1991002485A1 (en) * 1989-08-17 1991-03-07 Research Foundation Of The City University Of New York Microelectrodes and their use in a cathodic electrochemical current arrangement with telemetric application

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4025520A (en) * 1974-04-10 1977-05-24 Macfarlan Smith Limited Dehydrohalogenation of a 7-halodihydrocodeinone dialkyl ketal
WO1991002485A1 (en) * 1989-08-17 1991-03-07 Research Foundation Of The City University Of New York Microelectrodes and their use in a cathodic electrochemical current arrangement with telemetric application

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BRODERICK, P. A.: "In Vivo Electrochemical Studies of Rat Striatal Dopamine and Serotonine Release after Morphine", LIFE SCIENCES, vol. 36, 1985, pages 2269 - 2275, XP009022736 *
GOTO, K.; YAMAMOTO, I.: "(+)-Codeine and (+)-Morphine from Sinomenine", PROC. JPN. ACAD., vol. 30, 1954, pages 769 - 773, XP009022637 *
IIJIMA, I. ET AL.: "Studies in the (+)-Morphinan Series. 4. A Markedly Improved Synthesis of (+)-Morphine.", J. ORG. CHEM., vol. 43, no. 7, 1978, pages 1462 - 1463, XP001156547 *
J .ORG. CHEM.,SUPPLEMENTAL PAGES, vol. 62, 1997, pages 1 - 13, XP002275946 *
NICOLAOU K C ET AL: "A NEW METHOD FOR THE ONE-STEP SYNTHESIS OF A,BETA-UNSATURATED CARBONYL SYSTEMS FROM SATURATED ALCOHOLS COMPOUNDS", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, vol. 122, no. 31, 9 August 2000 (2000-08-09), pages 7596 - 7597, XP000937227, ISSN: 0002-7863 *
NICOLAOU; K. C. ET AL.: "Modulation of the Reactivity Profile of IBX by Ligand Complexation ...", ANGEW. CHEM. INT. ED., vol. 41, no. 6, 15 March 2002 (2002-03-15), pages 993 - 996, XP002275169 *
STRINGER, M. ET AL.: "d-Morphine, but not l-morphine, has low micromolar affinity for the non-competitive N-methyl-D-aspartate site in rat forebrain. ...", NEUROSCIENCE LETT., vol. 295, 2000, pages 21 - 24, XP002264370 *
WHITE, J. D. ET AL.: "Asymmetric Synthesis of (+)-Morphine. The Phenanthrene Route Revisited.", J. ORG. CHEM., vol. 62, 1997, pages 5250 - 5251, XP002275168 *

Also Published As

Publication number Publication date
AU2003263301A8 (en) 2004-03-29
WO2004022564A2 (en) 2004-03-18
GB2392670A (en) 2004-03-10
GB0220385D0 (en) 2002-10-09
AU2003263301A1 (en) 2004-03-29

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