561-25-1Relevant academic research and scientific papers
Selective Olefin Reduction in Thebaine Using Hydrazine Hydrate and O2 under Intensified Continuous Flow Conditions
Pieber, Bartholom?us,Cox, D. Phillip,Kappe, C. Oliver
, p. 376 - 385 (2016/03/04)
Hydrocodone, a high value active pharmaceutical ingredient (API), is usually produced in a semisynthetic pathway from morphine, codeine or thebaine. The latter alkaloid is an attractive precursor as it is not used as a remedy itself. The key step in this production route is a selective olefin reduction forming 8,14-dihydrothebaine which can be subsequently hydrolyzed to yield hydrocodone. Unfortunately, standard hydrogenation procedures cannot be applied due to severe selectivity problems. A transfer hydrogenation using in situ generated diimide is the only known alternative to achieve a selective transformation. The most (atom) economic generation of this highly unstable reducing agent is by oxidizing hydrazine hydrate (N2H4·H2O) with O2. In the past, this route was "forbidden" on an industrial scale due to its enormous explosion potential in batch. A continuous high-temperature/high-pressure methodology allows an efficient, safe, and scalable processing of the hazardous reaction mixture. The industrially relevant reduction was achieved by using four consecutive liquid feeds (of N2H4·H2O) and residence time units, resulting in a highly selective reduction within less than 1 h.
PROCESSES FOR MAKING HYDROCODONE, HYDROMORPHONE AND THEIR DERIVATIVES
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Paragraph 0082, (2015/09/28)
Improved processes for making hydrocodone and hydromorphone as well as their 8,14-dihydrothebaine and 8,14-dihydrooripavine derivatives and salts are disclosed.
PROCESSES FOR MAKING HYDROCODONE, HYDROMORPHONE AND THEIR DERIVATIVES
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Page/Page column 19, (2015/09/28)
Improved processes for making hydrocodone and hydromorphone as well as their 8,14-dihydrothebaine and 8,14-dihydrooripavine derivatives and salts are disclosed.
N-Demethylation of 6-Keto Morphinans
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Page/Page column 10, (2012/02/15)
The present invention provides processes for the demethylation of an N-methyl morphinan comprising a ketone functional group. In particular, the invention provides methods for the protection of the ketone functional group such that impurities are not generated during the demethylation of the N-methyl morphinan.
Methods for Producing Hydrocodone, Hydromorphone or a Derivative Thereof
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Page/Page column 11; 12, (2011/04/18)
The present disclosure generally relates to methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydromorphone, hydrocodone, or a derivative thereof, by means of a non-catalytic hydrogenation reaction of thebaine, oripavine or a derivative thereof, respectively, using a hydrazide reagent, followed by hydrolysis of the hydrogenated intermediate at a low temperature and for a short period of time. Additionally, the present disclosure relates to a composition comprising the desired hydromorphone, hydrocodone, or a derivative thereof, in combination with a 6-beta compound that is structurally related thereto.
Studies on regioselective hydrogenation of thebaine and its conversion to hydrocodone
Leisch, Hannes,Carroll, Robert J.,Hudlicky, Tomas,Cox, D. Phillip
, p. 3979 - 3981 (2008/02/04)
Thebaine was subjected to catalytic hydrogenation under a variety of conditions in order to determine the regioselectivity for C-6/C-7 versus C-8/C-14 olefin saturation.
Production of opioid analgesics
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Page/Page column 6, (2008/06/13)
The present invention includes a process for the manufacture of dihydrothebaine, dihydrocodeinone enol acetate, hydrocodone, and analogs thereof by reacting dihydrocodeine or analogs thereof with benzophenone in the presence of potassium tert-alkylate in a hydrocarbon solvent to generate a reaction mixture containing an enolate of the corresponding ketone, followed by addition of the reaction mixture to the electrophilic agent and isolation of the product.
