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US 8,524,904 B2Granted
Process for the preparation of 6-alpha-hydroxy-N-alkylated opiates
AssigneeMallinckrodt Inc.
InventorsChristopher W. Grote, Peter X. Wang, Tao Jiang, Gary L. Cantrell, Frank W. Moser, Catherine E. Thomasson
Life of this patent
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Abstract
The present invention is directed to the preparation of 6-hydroxy morphinans having formula (II) or N-alkylated 6-hydroxy morphinans having formula (III).
Claims12
A process wherein a 6-hydroxy morphinan (II) is reacted to form a 6-hydroxy-N-alkylated morphinan (III) having the formula:
- the process comprising reacting the 6-hydroxy morphinan (II) with an aldehyde of the formula CH(O)R9 in a solvent, followed by reducing with a hydride reducing agent, the 6-hydroxy morphinan (II) having the formula:
- wherein
- R1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR111;
- R2 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR211;
- R3 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR311;
- R7 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR711;
- R8 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR811;
- R9 is hydrogen, acyl, hydrocarbyl, substituted hydrocarbyl, or heterocyclo;
- R14 is hydrogen or hydroxy;
- R111 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R211 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R311 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R711 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R811 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- Z2 is >NH;
- and
- Z3 is >NCH2(R9),
- wherein the 6-hydroxy morphinan (II) and the 6-hydroxy-N-alkylated morphinan (III) have a 6-alpha-hydroxy moiety.
15 more elements
A process wherein a 6-hydroxy morphinan (II) is reacted to form a 6-hydroxy-N-alkylated morphinan (III) having the formula:
- the process comprising reacting the 6-hydroxy morphinan (II) with an aldehyde of the formula CH(O)R9 in a solvent, followed by reducing with a hydride reducing agent, the 6-hydroxy morphinan (II) having the formula:
- wherein
- R1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR111;
- R2 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR211;
- R3 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR311;
- R7 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR711;
- R8 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR811;
- R9 is hydrogen, acyl, hydrocarbyl, substituted hydrocarbyl, or heterocyclo;
- R14 is hydrogen or hydroxy;
- R111 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R211 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R311 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R711 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- R811 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group;
- Z2 is >NH;
- and
- Z3 is >NCH2(R9),
- wherein the 6-hydroxy morphinan (II) is prepared by reducing a 6-keto morphinan in the presence of a ruthenium, rhodium, or iridium asymmetric catalyst and a hydrogen source.
15 more elements
Dependencies are inferred from the claim text.