76-41-5

Basic information

• Product Name: OXYMORPHONE
• Synonyms: (14S)-14-Hydroxydihydromorphinone;14-Hydroxydihydromorphinone;3,14-dihydroxy-4,5-alpha-epoxy-17-methyl-morphinan-6-on;3,14-Dihydroxy-4,5-alpha-epoxy-17-methylmorphinan-6-one;4,5alpha-Epoxy-3,14-dihydroxy-17-methylmorphinan-6-one;5-epoxy-3,14-dihydroxy-17-methyl-(5-alpha)-morphinan-6-on;7,8-Dihydro-14-hydroxymorphinone;Dihydro-14-hydroxymorphinone
• CAS NO: 76-41-5
• Molecular Formula: C₁₇H₁₉NO₄
• Molecular Weight: 301.34
• EINECS: 200-959-7
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Chiral Reagents
• Mol File: 76-41-5.mol

Chemical Properties

• Melting Point: 248-249°C (dec)
• Boiling Point: 518.627 °C at 760 mmHg
• Flash Point: 9℃
• Appearance: Crystalline Solid
• Density: 1.503 g/cm³
• Storage Temp.: Controlled Substance, -20°C Freezer
• PKA: pKa 8.50 (Uncertain);9.33 (Uncertain)
• CAS DataBase Reference: OXYMORPHONE(CAS DataBase Reference)
• NIST Chemistry Reference: OXYMORPHONE(76-41-5)
• EPA Substance Registry System: OXYMORPHONE(76-41-5)

Safety Data

• Hazard Codes: F,T,T+
• Statements: 11-23/24/25-39/23/24/25-26/27/28
• Safety Statements: 16-36/37-45-36/37/39-22
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 1
• Hazardous Substances Data: 76-41-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Oxymorphone is used as an analgesic for the management of moderate to severe pain. Its potency and various formulations make it a suitable option for patients suffering from chronic pain.
Used in Pain Management:
Oxymorphone is used as a potent pain reliever for patients with moderate to severe pain, providing effective pain control and improving the quality of life for those in need.
Used in Extended Release Formulations:
The FDA-approved sustained-release formulation of oxymorphone (Opana ER) offers 12-hour coverage, providing an additional option for patients with chronic pain, ensuring consistent pain relief throughout the day.
Used in Side Effect Management:
The side effect profile of oxymorphone's extended-release formulations is similar to that of morphine and oxycodone, allowing healthcare providers to consider it as an alternative option for pain management without significant differences in side effects.

Originator

Numorphan,Endo, US ,1959

Manufacturing Process

Thebaine is dissolved in aqueous formic acid and treated with 30% H2O2; neutralization with aqueous ammonia gives 14-hydroxycodeinone. It is hydrogenated to give oxycodone. 90 ml of concentrated hydrobromic acid are heated to 90°C. 9 grams of 14-hydroxydihydrocodeinone (oxycodone) are then added under stirring and the mixture is quickly heated to 116°C and kept at this temperature under reflux condenser for 20 minutes, with continued stirring. The resulting brown solution is diluted with about 90 ml of water and chilled with ice. Aqueous 10% sodium hydroxide solution is now added to alkaline reaction and the liquid is extracted 3 times with 100 cc portions of chloroform. The layers are separated and the aqueous phase is filtered and acidified by the addition of concentrated aqueous hydrochloric acid, treated with charcoal and filtered. The filtrate is treated with concentrated aqueous ammonia until the mixture gives a pink color on phenolphthalein paper. The liquid is extracted seven times with 100 cc portions of chloroform, the extracts are combined, dried with anhydrous sodium sulfate and evaporated. The residue is dissolved in ethanol by refluxing and the ethanol evaporated nearly to dryness. 100 cc of benzene are then added, the mixture is refluxed for ? hour and set aside for crystallization. After cooling, the desired compound is collected by filtration, 2.3 grams of a white crystalline powder are obtained; MP 245° to 247°C. This powder consisting of 14-hydroxydihydromorphinone can be purified by recrystallization from benzene, ethylacetate or ethanol. From benzene it generally forms diamond shaped platelets, while needles are obtained from ethylacetate. On heating, the crystals are discolored from about 200°C on, and melt at 246° to 247°C to a black liquid, which decomposes with strong volume increase if the temperature is raised further by a few degrees.

Biological Functions

Oxymorphone is 10 times as potent as morphine, with actions similar to those of hydromorphone. Oxymorphone, however, has little antitussive activity, and as such is a useful analgesic in patients with pulmonary disease who need to retain the ability to cough.

InChI:InChI=1S/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3

Upstream product

• 76-42-6 Oxycodone 
• 59-51-8 DL-methionine 
• 357-07-3 oxymorphone hydrochloride 
• 41135-98-2 14-hydroxymorphinone 
• 1234788-76-1 oxymorphone-N-oxide hydrochloride 
• 57093-47-7 3-acetyloripavine 
• 115-37-7 thebaine 
• 467-04-9 oripavine 
• 124-90-3 oxycodone hydrochloride 
• 2859-02-1 oxycodone ethyleneglycol ketal 
• 70509-92-1 14-acetoxy-4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one 
• 76-42-6 C₁₈H₂₁NO₄ 

Downstream Products

• 852836-61-4 3-benzyloxy-4,5α-epoxy-14-hydroxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) 
• 852836-62-5 14-allyloxy-3-benzyloxy-4,5α-epoxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) 
• 852836-63-6 3-benzyloxy-14-(2',6'-dichlorobenzyloxy)-4,5α-epoxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) 
• 1050618-42-2 (S)-17-(3'-phenylbut-2'-ynyl)-4,5α-epoxy-3,14-di-hydroxy-17-methyl-6-oxomorphinanium iodide 
• 16590-41-3 Naltrexone 
• 4778-94-3 4,5α-epoxy-3,14-dihydroxy-17-phenethyl-morphinan-6-one 
• 503091-11-0 C₂₅H₂₇NO₄ 
• 73697-35-5 oxymorphazone 
• 73986-27-3 C₂₄H₂₆N₂O₃ 
• 5868-03-1 (-)-3-(benzyloxy)-4,5-epoxy-14-hydroxy-N-methylmorphinan-6-one 
• 64643-76-1 4,5α-epoxy-3,14-diacetoxy-6-oxo-17-methylmorphinan 
• 81165-16-4 C₂₄H₂₃N₅O₄ 
• 16676-29-2 naltrexone Hydrochloride 
• 20594-83-6 nalbuphine 

Relevant articles and documents

An Integrated Continuous-Flow Synthesis of a Key Oxazolidine Intermediate to Noroxymorphone from Naturally Occurring Opioids

A telescoped procedure for the direct preparation of an advanced intermediate towards noroxymorphone from the naturally occurring alkaloids oripavine and thebaine is presented. The reaction procedure involves an intensified continuous-flow hydroxylation, followed by a continuous solvent switch and hydrogenation in a packed-bed hydrogenator (H-Cube). The obtained reaction mixture, containing oxymorphone as intermediate in excellent yield and purity, can be then directly converted into the desired noroxymorphone oxazolidine intermediate through palladium catalyzed N-methyl oxidation.

Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers

The functional interactions between opioid and chemokine receptors have been implicated in the pathological process of chronic pain. Mounting studies have indicated the possibility that a MOR-CXCR4 heterodimer may be involved in nociception and related ph

AN IMPROVED PROCESS FOR O-DEMETHYLATING METHOXY SUBSTITUTED MORPHINAN-6-ONE DERIVATIVES USING BORON-BASED COMPLEXES

The present invention discloses an improved process for O-demethylation of methoxy-substituted morphinan-6-one derivatives using boron-based complex as a demethylating boron complex in an inert reaction solvent.

PROCESS FOR THE PREPARATION OF MORPHINANE COMPOUNDS

The invention describes the process of catalytic O-demethylation of 3-methoxy-morphinane compounds using boron tribromide. Addition of catalysts reduces the reaction time, improves reacting the substrate to give the product in very good purity and yield. The said approach can be used, for example, for the preparation of oxymorphone, naltrexone, naloxone and nalbuphine from their respective O-methyl derivatives.

Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.

ABUSE-DETERRENT PHARMACEUTICAL COMPOSITIONS

Disclosed are pharmaceutical compositions comprising oxycodone and an oxycodone-processing enzyme, wherein oxycodone is contained in the pharmaceutical composition in a storage stable, enzyme-reactive state and under conditions wherein no enzymatic activity acts on oxycodone.

PROCESS FOR OBTAINING 3,14-DIACETYLOXYMORPHONE FROM ORIPAVINE

The present invention relates to a new process for obtaining 3,14-diacetyloxymorphone from oripavine, a process to transform the obtained 3,14-diacetyloxymorphone into a noroxymorphone and a process to transform said noroxymorphone into naloxone, naltrexone, nalbuphine, nalfurafine or nalmefene.

Design and Development of Pd-Catalyzed Aerobic N-Demethylation Strategies for the Synthesis of Noroxymorphone in Continuous Flow Mode

Strategies for the generation of noroxymorphone from 14-hydroxymorphinone are presented. Noroxymorphone is the key intermediate in the synthesis of various opioid antagonists, including naloxone, naltrexone, and nalmefene, as well as mixed agonists-antagonists such as nalbuphine. The transformation requires removal of the N-methyl group from the naturally occurring opiates and double-bond hydrogenation. The pivotal reaction step thereby is an N-methyl oxidation with colloidal palladium(0) as catalyst and pure oxygen as terminal oxidant. The reaction produces a 1,3-oxazolidine intermediate, which can be readily hydrolyzed to the corresponding secondary amine. Different reaction sequences and the use of various phenol protecting groups were explored. The most direct route consumes only H2, O2, and H2O as stoichiometric reagents and produces only H2O as a byproduct. Challenges inherent to gas/liquid reactions with oxygen as oxidant have been addressed by developing a continuous flow process.

PROCESS FOR IMPROVED OXYMORPHONE SYNTHESIS

Processes for preparing oxymorphone are provided. Said processes encompass a step which is a hydrogenation of an 14-hydroxymorphinone salt in the presence of trifluoroacetic acid and/or a glycol.

PROCESSES AND OXAZOLIDINE-CONTAINING INTERMEDIATES FOR THE PREPARATION OF MORPHINE ANALOGS AND DERIVATIVES

The present invention relates to processes useful in the preparation of morphine analogs and derivatives, such as naltrexone, naloxone and nalbuphine and intermediates in the synthesis of said morphine analogs and derivatives. In a particular example, the process begins with for example oxymorphone, oxycodone, 14-hydroxycodeinone or 14- hydroxymorphinone, and includes the formation of an oxazolidine-containing intermediate using catalytic oxidation.