Preparation of saturated ketone morphinan compounds having low metal content
Inventors
Jiang, Tao • Wang, Peter X. • Berberich, David W.
Assignees
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Publication Number
US-8563725-B2
Publication Date
2013-10-22
Expiration Date
Abstract
The present invention provides processes for the preparation of saturated ketone morphinan compounds from a morphinan comprising an allyl alcohol ring moiety, wherein the final product has a low metal content. In particular, the invention provides processes that utilize isomerization reactions catalyzed by transition metal catalysts and the subsequent removal of the transition metal using metal scavengers.
Core Innovation
The invention describes a process for preparing a compound having Formula (II) in a substantially metal-free form. The process includes contacting a compound having Formula (I) with a transition metal catalyst to form a reaction product comprising the compound having Formula (II), and then contacting the reaction product with a metal scavenger that binds the transition metal catalyst.
The core process yields substantially metal-free compound having Formula (II). The transition metal catalyst is used to form a reaction product in step (a), and the metal scavenger is used to bind the transition metal catalyst and thereby yield the substantially metal-free compound in step (b).
The document further emphasizes low metal content in the final compound, including embodiments that report low ruthenium content. The process is described as broadly applicable to producing substantially metal-free hydromorphone/hydrocodone derived from morphine/codeine via saturated ketone morphinan conversion.
Claims Coverage
The independent claim is directed to a two-step contacting process that converts a Formula (I) compound to a substantially metal-free Formula (II) compound using a transition metal catalyst followed by a metal scavenger that binds the transition metal catalyst. The independent inventive coverage contains two core inventive actions in sequence.
Substantially metal-free Formula (II) via transition metal catalysis followed by metal scavenging
A process for preparing a compound having Formula (II) wherein the compound having Formula (II) is substantially metal-free, comprising contacting a compound having Formula (I) with a transition metal catalyst to form a reaction product comprising the compound having Formula (II), and contacting the reaction product of step (a) with a metal scavenger such that the metal scavenger binds the transition metal catalyst, thereby yielding the substantially metal-free compound having Formula (II).
The inventive concept is the sequential combination of transition metal-catalyzed formation of the Formula (II) compound followed by contacting with a metal scavenger that binds the transition metal catalyst, yielding a substantially metal-free Formula (II) product.
Stated Advantages
Produces a compound having Formula (II) that is substantially metal-free.
Targets low transition-metal contamination in the substantially metal-free compound having Formula (II).
Documented Applications
Producing substantially metal-free hydromorphone/hydrocodone from morphine/codeine through conversion to saturated ketone morphinans using the described one-pot transition-metal-catalyzed isomerization followed by transition-metal scavenging.
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