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US 12,643,908 B2Granted
Process for the synthesis of noroxymorphone from morphine
AssigneeNavin Saxena Research & Technology Pvt. Ltd.
InventorsDmitry Gorbachev, Hon Wai Lam, Aakarsh Saxena, Navin Satyapal Saxena
Life of this patent
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Abstract
The present invention relates to a novel, efficient, pot- and atom-economical, and industrially applicable process for converting morphine to noroxymorphone using reagents and solvents of lesser toxicity and lower cost with respect to those used in the prior art.
Claims19
A process for preparing noroxymorphone from morphine comprising:
- 1) reacting morphine of formula (II) to obtain a compound of formula (III);
- 2a) oxidizing the compound of formula (III) with an oxidizing agent to obtain a compound of formula (IV);
- 2b) acylating the compound of formula (IV) with an acylation agent to obtain a compound of formula (V);
- 3a) subjecting the compound of formula (V) to peroxy oxidation to obtain a compound of formula (VI);
- 3b) reducing the compound of formula (VI) to obtain a compound of formula (VII);
- and
- 4) hydrolyzing the compound of formula (VII) to obtain noroxymorphone of formula (I);
- wherein R1 and R2 independently are a substituted or unsubstituted alkyl group with 1 to 20 carbon atoms, or a substituted or unsubstituted aryl group, or a substituted or unsubstituted alkylaryl group with 1 to 20 carbon atoms, or a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, or a substituted or unsubstituted alkoxycarbonyl group with 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted aryloxycarbonyl group or a substituted or unsubstituted alkylaryloxycarbonyl group with 1 to 20 carbon atoms in the alkyl residue, or a cyanide group, or a silyl group of formula Si(R4)3, wherein the groups R4 can be the same or different and are each selected from substituted or unsubstituted alkyl groups having 1 to 6 carbon atoms and substituted or unsubstituted aryl groups, respectively, and wherein R3 is a substituted or unsubstituted alkylcarbonyl group having 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted alkylarylcarbonyl group having 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted arylcarbonyl group, or a substituted or unsubstituted alkenylcarbonyl group having 2 to 20 carbon atoms, respectively;
- wherein step 2a is conducted by oxidizing the compound of formula III with an acyclic or cyclic organic acid anhydride and a dialkyl sulfoxide at or above room temperature;
- wherein step 2a and step 2b are optionally combined into a one-pot single-step transformation, and
- wherein step 3a and step 3b are optionally combined into a one-pot single-step transformation.
8 more elements
A process for preparing noroxymorphone from morphine comprising:
- 1) reacting morphine of formula (II) to obtain a compound of formula (III);
- 2) in a first one-pot single step transformation, oxidizing the compound of formula (III) with an Albright-Goldman oxidizing agent using Albright-Goldman oxidation conditions to obtain a compound of formula (IV), and acylating the compound of formula (IV) with an acylation agent to obtain a compound of formula (V);
- 3) in a second one-pot single step transformation, subjecting the compound of formula (V) to peroxy oxidation to obtain a compound of formula (VI), and reducing the compound of formula (VI) to obtain a compound of formula (VII);
- and
- 4) hydrolyzing the compound of formula (VII) to obtain noroxymorphone of formula (I);
- wherein R1 and R2 independently are a substituted or unsubstituted alkyl group with 1 to 20 carbon atoms, or a substituted or unsubstituted aryl group, or a substituted or unsubstituted alkylaryl group with 1 to 20 carbon atoms, or a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, or a substituted or unsubstituted alkoxycarbonyl group with 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted aryloxycarbonyl group or a substituted or unsubstituted alkylaryloxycarbonyl group with 1 to 20 carbon atoms in the alkyl residue, or a cyanide group, or a silyl group of formula Si(R4)3, wherein the groups R4 can be the same or different and are each selected from substituted or unsubstituted alkyl groups having 1 to 6 carbon atoms and substituted or unsubstituted aryl groups, respectively, and wherein R3 is a substituted or unsubstituted alkylcarbonyl group having 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted alkylarylcarbonyl group having 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted arylcarbonyl group, or a substituted or unsubstituted alkenylcarbonyl group having 2 to 20 carbon atoms, respectively.
3 more elements
Dependencies are inferred from the claim text.