ZA200401016B - Process for the preparation of a 14-hydroxynormorphinone derivative. - Google Patents

Process for the preparation of a 14-hydroxynormorphinone derivative. Download PDF

Info

Publication number: ZA200401016B
Authority: ZA; South Africa
Prior art keywords: formula; derivative; benzyl; morphine; hydroxynormorphinone
Prior art date: 2001-08-23

Application number

ZA200401016A

Other languages

English (en)

Inventor

Joannes Theodorus Mari Linders

Pieter Vrijhof

Original Assignee

Akzo Nobel Nv

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.)

2001-08-23

Filing date

2004-02-06

Publication date

2004-10-19

2004-02-06 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2004-10-19 Publication of ZA200401016B publication Critical patent/ZA200401016B/en

Links

238000000034 method Methods 0.000 title claims description 53
WJZVCRUPHQAKSZ-IPOQPSJVSA-N (4r,4as,7ar,12bs)-4a,9-dihydroxy-1,2,3,4,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one Chemical class O=C([C@@H]1O2)C=C[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4 WJZVCRUPHQAKSZ-IPOQPSJVSA-N 0.000 title claims description 25
238000002360 preparation method Methods 0.000 title claims description 9
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 33
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
230000001590 oxidative effect Effects 0.000 claims description 21
239000007800 oxidant agent Substances 0.000 claims description 18
PFBSOANQDDTNGJ-YNHQPCIGSA-N morphinone Chemical class O([C@H]1C(C=C[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O PFBSOANQDDTNGJ-YNHQPCIGSA-N 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
150000001875 compounds Chemical class 0.000 claims description 14
HLMSIZPQBSYUNL-IPOQPSJVSA-N Noroxymorphone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4 HLMSIZPQBSYUNL-IPOQPSJVSA-N 0.000 claims description 13
238000004519 manufacturing process Methods 0.000 claims description 11
229960005181 morphine Drugs 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
230000003647 oxidation Effects 0.000 claims description 8
238000007254 oxidation reaction Methods 0.000 claims description 8
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
239000001632 sodium acetate Substances 0.000 claims description 7
235000017281 sodium acetate Nutrition 0.000 claims description 7
XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 6
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
JHWIEAWILPSRMU-UHFFFAOYSA-N 2-methyl-3-pyrimidin-4-ylpropanoic acid Chemical group OC(=O)C(C)CC1=CC=NC=N1 JHWIEAWILPSRMU-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 4
125000000746 allylic group Chemical group 0.000 claims description 3
125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 3
235000017168 chlorine Nutrition 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000000468 ketone group Chemical group 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
235000011056 potassium acetate Nutrition 0.000 claims description 3
229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
235000011009 potassium phosphates Nutrition 0.000 claims description 3
239000001488 sodium phosphate Substances 0.000 claims description 3
229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
235000011008 sodium phosphates Nutrition 0.000 claims description 3
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
229920002554 vinyl polymer Chemical group 0.000 claims description 3
229910017052 cobalt Inorganic materials 0.000 claims description 2
239000010941 cobalt Substances 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
239000000243 solution Substances 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000002585 base Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
FQXXSQDCDRQNQE-UHFFFAOYSA-N markiertes Thebain Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(OC)C5=C4C23C1O5 FQXXSQDCDRQNQE-UHFFFAOYSA-N 0.000 description 4
229930003945 thebaine Natural products 0.000 description 4
FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 4
-1 CoF Chemical class 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
238000004090 dissolution Methods 0.000 description 3
SBUHJBVHHLYTOX-RTOPKKFASA-N ethyl (4R,4aS,7aR,12bS)-4a-hydroxy-7-oxo-9-phenylmethoxy-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-3-carboxylate Chemical compound C(C)OC(=O)N1[C@H]2[C@@]3(C=CC([C@H]4[C@@]3(C=3C(=C(C=CC=3C2)OCC2=CC=CC=C2)O4)CC1)=O)O SBUHJBVHHLYTOX-RTOPKKFASA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000000203 mixture Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
239000003570 air Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
238000010533 azeotropic distillation Methods 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
229940005483 opioid analgesics Drugs 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
238000003756 stirring Methods 0.000 description 2
YYCRAERBSFHMPL-XFKAJCMBSA-N (4r,4as,7ar,12bs)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one Chemical compound O=C([C@@H]1O2)C=C[C@@]3(O)[C@]4([H])N(C)CC[C@]13C1=C2C(OC)=CC=C1C4 YYCRAERBSFHMPL-XFKAJCMBSA-N 0.000 description 1
WYMBHLXUDPDGQJ-BRJGLHKUSA-N (4r,4as,7s,7ar,12bs)-3-methyl-1,2,4,7,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7,9-triol Chemical class O([C@H]1[C@H](C=C[C@]23O)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WYMBHLXUDPDGQJ-BRJGLHKUSA-N 0.000 description 1
YYCRAERBSFHMPL-UHFFFAOYSA-N 14beta-Hydroxycodeinone Natural products O1C2C(=O)C=CC3(O)C4CC5=CC=C(OC)C1=C5C23CCN4C YYCRAERBSFHMPL-UHFFFAOYSA-N 0.000 description 1
239000003810 Jones reagent Substances 0.000 description 1
239000008896 Opium Substances 0.000 description 1
235000008753 Papaver somniferum Nutrition 0.000 description 1
240000001090 Papaver somniferum Species 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 description 1
XYYVYLMBEZUESM-CMKMFDCUSA-N codeinone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=CC(=O)[C@@H]1OC1=C2C3=CC=C1OC XYYVYLMBEZUESM-CMKMFDCUSA-N 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
229960004592 isopropanol Drugs 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
229960004127 naloxone Drugs 0.000 description 1
DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
229960003086 naltrexone Drugs 0.000 description 1
229960001027 opium Drugs 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229910001927 ruthenium tetroxide Inorganic materials 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
229960002415 trichloroethylene Drugs 0.000 description 1
UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1

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:
- C07D489/06—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 a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pain & Pain Management (AREA)
Pharmacology & Pharmacy (AREA)
Rheumatology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Saccharide Compounds (AREA)

ZA200401016A 2001-08-23 2004-02-06 Process for the preparation of a 14-hydroxynormorphinone derivative. ZA200401016B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP01203187		2001-08-23

Publications (1)

Publication Number	Publication Date
ZA200401016B true ZA200401016B (en)	2004-10-19

Family

ID=8180821

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200401016A ZA200401016B (en)	2001-08-23	2004-02-06	Process for the preparation of a 14-hydroxynormorphinone derivative.

Country Status (25)

Country	Link
US (1)	US7435817B2 (fr)
EP (1)	EP1421085B1 (fr)
JP (1)	JP4559730B2 (fr)
KR (1)	KR100901402B1 (fr)
CN (1)	CN1271072C (fr)
AR (1)	AR035289A1 (fr)
AT (1)	ATE466016T1 (fr)
AU (1)	AU2002331163B2 (fr)
BR (1)	BRPI0211899B8 (fr)
CA (1)	CA2457671C (fr)
DE (1)	DE60236171D1 (fr)
EC (1)	ECSP044984A (fr)
ES (1)	ES2345327T3 (fr)
HR (1)	HRP20040161A2 (fr)
HU (1)	HUP0401600A3 (fr)
IL (1)	IL160193A0 (fr)
IS (1)	IS7153A (fr)
MX (1)	MXPA04001647A (fr)
NO (1)	NO328655B1 (fr)
NZ (1)	NZ531152A (fr)
PE (1)	PE20030460A1 (fr)
PL (1)	PL368732A1 (fr)
RU (1)	RU2297419C2 (fr)
WO (1)	WO2003018588A2 (fr)
ZA (1)	ZA200401016B (fr)

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Publication number	Priority date	Publication date	Assignee	Title
WO2006126529A1 (fr) *	2005-05-25	2006-11-30	Shionogi & Co., Ltd.	Derive de morphinane substitue en position 7 par un carbamoyle et insature en positions 6 et 7
ES2357216T3 (es) *	2005-06-16	2011-04-20	Mallinckrodt, Inc.	Una ruta de síntesis de 14-hidroxil-opiáceos a través de 1-halo-tebaína o análogos.
CA2681740A1 (fr) *	2007-03-23	2008-10-02	Mallinckrodt Inc.	Preparation amelioree d'oxymorphone a partir d'oripavine
CN101033228B (zh) *	2007-04-04	2010-05-19	复旦大学	14-羟基-7,8-二氢降吗啡酮的制备方法
ES2423180T3 (es)	2007-04-16	2013-09-18	Mallinckrodt Llc	Nueva reducción de opiáceos mediante reacción de transferencia de hidrógeno catalítica
NZ586187A (en) *	2007-12-17	2013-07-26	Mallinckrodt Llc	Processes for the synthesis of sinomenine derivatives and their intermediate
CN101896487A (zh)	2007-12-17	2010-11-24	马林克罗特公司	N-甲基吗啡喃的n-脱甲基化
NZ586203A (en) *	2007-12-17	2012-10-26	Mallinckrodt Llc	Process and compounds for the production of (+) opiates
CA2798885C (fr)	2010-05-10	2014-11-18	Euro-Celtique S.A.	Combinaison de granules charges de principe actif et de principes actifs supplementaires
BR112012028773A2 (pt)	2010-05-10	2016-07-19	Euro Celtique Sa	composições farmacêuticas compreendendo hidromorfona e naloxona
AU2011252040C1 (en)	2010-05-10	2015-04-02	Euro-Celtique S.A.	Manufacturing of active-free granules and tablets comprising the same
EP2580201B1 (fr)	2010-06-11	2017-08-02	Rhodes Technologies	Procédés catalysés par métal de transition pour la préparation de composés de n-allyle et utilisation de ceux-ci
TWI471289B (zh)	2010-06-11	2015-02-01	Rhodes Technologies	使三級胺進行ｎ－脫烷反應之方法
BR112014005421A2 (pt)	2011-09-08	2017-04-04	Mallinckrodt Llc	produção de alcaloides sem o isolamento de intermediários
WO2015015146A1 (fr) *	2013-08-02	2015-02-05	Johnson Matthey Public Limited Company	Procédé de préparation d'oxymorphone
EP3068397A1 (fr)	2013-11-13	2016-09-21	Euro-Celtique S.A.	Hydromorphone et naloxone utilisées pour le traitement de la douleur et du syndrome de dysfonctionnement intestinal dû aux opioïdes
CN114621238B (zh) *	2020-12-10	2026-02-03	鲁南制药集团股份有限公司	一种制备纳呋拉啡的方法

Family Cites Families (5)

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Publication number	Priority date	Publication date	Assignee	Title
IT1199871B (it)	1984-03-27	1989-01-05	Mallinckrodt Inc	Procedimento per la preparazione di norossimorfone dalla morfina e composti intermedi per tale procedimento
US5112975A (en) *	1984-03-27	1992-05-12	Mallinckrodt Specialty Chemicals Company	Preparation of noroxymorphone from morphine
US4668685A (en) *	1984-07-05	1987-05-26	E.I. Du Pont De Nemours And Company	Substituted benzoate ester prodrug derivatives of 3-hydroxymorphinans, which are analgesics or narcotic antagonists
US5869669A (en) *	1996-07-26	1999-02-09	Penick Corporation	Preparation of 14-hydroxynormorphinones from normorphinone dienol acylates
WO2000066588A1 (fr) *	1999-05-05	2000-11-09	The Government Of The United States Of America, Represented By The Secretary, Departmentof Health A Nd Human Services	Oxydation directe d'opioides a la position c-14

2002
- 2002-08-15 KR KR1020047002513A patent/KR100901402B1/ko not_active Expired - Fee Related
- 2002-08-15 MX MXPA04001647A patent/MXPA04001647A/es active IP Right Grant
- 2002-08-15 NZ NZ531152A patent/NZ531152A/en not_active IP Right Cessation
- 2002-08-15 RU RU2004108210/04A patent/RU2297419C2/ru active
- 2002-08-15 ES ES02767405T patent/ES2345327T3/es not_active Expired - Lifetime
- 2002-08-15 PL PL02368732A patent/PL368732A1/xx not_active Application Discontinuation
- 2002-08-15 WO PCT/EP2002/009280 patent/WO2003018588A2/fr not_active Ceased
- 2002-08-15 DE DE60236171T patent/DE60236171D1/de not_active Expired - Lifetime
- 2002-08-15 AU AU2002331163A patent/AU2002331163B2/en not_active Expired
- 2002-08-15 HR HR20040161A patent/HRP20040161A2/xx not_active Application Discontinuation
- 2002-08-15 HU HU0401600A patent/HUP0401600A3/hu unknown
- 2002-08-15 CN CNB028163524A patent/CN1271072C/zh not_active Expired - Lifetime
- 2002-08-15 IL IL16019302A patent/IL160193A0/xx unknown
- 2002-08-15 BR BRPI0211899A patent/BRPI0211899B8/pt not_active IP Right Cessation
- 2002-08-15 US US10/487,884 patent/US7435817B2/en not_active Expired - Lifetime
- 2002-08-15 CA CA2457671A patent/CA2457671C/fr not_active Expired - Lifetime
- 2002-08-15 JP JP2003523248A patent/JP4559730B2/ja not_active Expired - Lifetime
- 2002-08-15 AT AT02767405T patent/ATE466016T1/de active
- 2002-08-15 EP EP02767405A patent/EP1421085B1/fr not_active Expired - Lifetime
- 2002-08-21 AR ARP020103130A patent/AR035289A1/es active IP Right Grant
- 2002-08-21 PE PE2002000800A patent/PE20030460A1/es not_active Application Discontinuation
2004
- 2004-02-06 ZA ZA200401016A patent/ZA200401016B/en unknown
- 2004-02-13 IS IS7153A patent/IS7153A/is unknown
- 2004-02-19 EC EC2004004984A patent/ECSP044984A/es unknown
- 2004-02-19 NO NO20040724A patent/NO328655B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
AR035289A1 (es)	2004-05-05
ES2345327T3 (es)	2010-09-21
HUP0401600A3 (en)	2008-05-28
RU2004108210A (ru)	2005-04-10
AU2002331163B2 (en)	2008-02-21
IL160193A0 (en)	2004-07-25
KR20040027950A (ko)	2004-04-01
MXPA04001647A (es)	2004-05-31
PE20030460A1 (es)	2003-05-15
CN1271072C (zh)	2006-08-23
US20050038250A1 (en)	2005-02-17
WO2003018588B1 (fr)	2004-02-26
BR0211899A (pt)	2004-09-21
RU2297419C2 (ru)	2007-04-20
ATE466016T1 (de)	2010-05-15
KR100901402B1 (ko)	2009-06-05
HUP0401600A2 (hu)	2004-11-29
NZ531152A (en)	2005-11-25
DE60236171D1 (de)	2010-06-10
HK1063803A1 (en)	2005-01-14
US7435817B2 (en)	2008-10-14
NO328655B1 (no)	2010-04-19
HRP20040161A2 (en)	2004-06-30
EP1421085A2 (fr)	2004-05-26
IS7153A (is)	2004-02-13
WO2003018588A3 (fr)	2003-11-27
JP2005502670A (ja)	2005-01-27
NO20040724L (no)	2004-02-19
BR0211899B1 (pt)	2014-01-21
CA2457671C (fr)	2011-02-15
BRPI0211899B8 (pt)	2021-05-25
JP4559730B2 (ja)	2010-10-13
PL368732A1 (en)	2005-04-04
ECSP044984A (es)	2004-04-28
CA2457671A1 (fr)	2003-03-06
EP1421085B1 (fr)	2010-04-28
WO2003018588A2 (fr)	2003-03-06
CN1545517A (zh)	2004-11-10

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AU2002331163A1 (en)	2003-06-05	Process for the Preparation of a 14-hydroxynormorphinone Compound
EP2112153B1 (fr)	2010-11-10	Procédé de réduction de cétones insaturées alpha et bêta dans des compositions d'opioides
US7071336B2 (en)	2006-07-04	Process for manufacturing opioid analgesics
EP1664061B1 (fr)	2017-03-15	Procede de synthese de composes de morphinane et leurs intermediaires
Barber et al.	1976	Conversion of thebaine to codeine
US8106201B2 (en)	2012-01-31	Process for the synthesis of morphinane compounds and intermediates thereof
US20230357257A1 (en)	2023-11-09	Novel process for the synthesis of noroxymorphone from morphine
HK1063803B (en)	2010-08-06	Process for the preparation of a 14-hydroxynormorphinone derivative
US6790959B1 (en)	2004-09-14	Process for manufacturing thebaine
TWI292761B (en)	2008-01-21	C-14 oxidation of morphine derivatives
AU2004274038B2 (en)	2011-03-10	Process for the synthesis of morphinane compounds and intermediates thereof
HK1135107B (en)	2011-01-14	Method of reducing alpha, beta- unsaturated ketones in opioid compositions
HK1111695B (en)	2009-08-07	Method of reducing alpha, beta- unsaturated ketones in opioid compositions
HU181372B (hu)	1983-07-28	Eljárás új 11-bróm-14-oxo-E-homo-eburnán származékok előállítására