Processes for preparing morphinan-6-one products with low levels of alpha beta-unsaturated compounds

A process for the preparation of a morphinan-6-one product, the process comprising:

• forming a reaction mixture comprising a morphinan-6-one compound and an a,(3-unsaturated ketone compound;
• treating the reaction mixture with a non-thiol sulfur-containing compound to reduce the concentration of the α,β-unsaturated ketone compound in the reaction mixture;
• and
• recovering the morphinan-6-one compound to produce the morphinan-6-one product;
• wherein
• the morphinan-6-one compound corresponds to Formula (2):
• the α,β-unsaturated ketone compound corresponds to Formula (3):
• X is —N(R17)— or —N+(R17aR17b)—;
• R1 and R2 are independently selected from hydrogen, substituted and unsubstituted acyl, acyloxy, alkenyl, alkoxy, alkoxyaryl, alkyl, alkylamino, alkynyl, amino, aryl, arylalkoxy, carboalkoxy, carbonyl, carboxyalkenyl, carboxyalkyl, carboxyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylether, halo, haloalkoxy, haloalkyl, heteroaryl, heterocyclic, hydroxyalkyl, hydroxyl, or nitro;
• R3 is hydrogen, hydroxy, protected hydroxy, alkoxy, or acyloxy;
• R10 is hydrogen, hydroxy, protected hydroxy, halo, keto, tosyl, mesyl, or trifluoromesyl;
• R14 is hydrogen, hydroxy, or protected hydroxy;
• R17 is hydrogen, alkyl, cycloalkyl, alkylcarboxy, alkylenecycloalkyl, alkoxycarbonyl, allyl, alkenyl, acyl, aryl, formyl, formyl ester, formamide, benzyl, or an amino protecting group;
• R17a and R17b are independently selected from hydrogen, alkyl, alkenyl, allyl, cycloalkyl, aryl, or benzylyl, and the morphinan-6-one product comprises less than about 0.1% (by weight morphinan-6-one product) of the α,β-unsaturated ketone compound.

A process for producing a morphinan-6-one product, the process comprising:

• forming a reaction mixture comprising an α,β-unsaturated ketone compound;
• treating the reaction mixture with a non-thiol sulfur-containing compound to reduce the α,β-unsaturated ketone to form a morphinan-6-one compound;
• and
• recovering the morphinan-6-one compound to form the morphinan-6-one product;
• wherein
• the morphinan-6-one compound corresponds to Formula (2):
• the α,β-unsaturated ketone compound corresponds to Formula (3):
• X is —N(R17)— or —N+(R17aR17b)—;
• R1 and R2 are independently selected from hydrogen, substituted and unsubstituted acyl, acyloxy, alkenyl, alkoxy, alkoxyaryl, alkyl, alkylamino, alkynyl, amino, aryl, arylalkoxy, carboalkoxy, carbonyl, carboxyalkenyl, carboxyalkyl, carboxyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylether, halo, haloalkoxy, haloalkyl, heteroaryl, heterocyclic, hydroxyalkyl, hydroxyl, or nitro;
• R3 is hydrogen, hydroxy, protected hydroxy, alkoxy, or acyloxy;
• R10 is hydrogen, hydroxy, protected hydroxy, halo, keto, tosyl, mesyl, or trifluoromesyl;
• R14 is hydrogen, hydroxy, or protected hydroxy;
• R17 is hydrogen, alkyl, cycloalkyl, alkylcarboxy, alkylenecycloalkyl, alkoxycarbonyl, allyl, alkenyl, acyl, aryl, formyl, formyl ester, formamide, benzyl, or an amino protecting group;
• and
• R17a and R17b are independently selected from hydrogen, alkyl, alkenyl, allyl, cycloalkyl, aryl, or benzylyl.