Abstract: For the synthesis of 3-methylnaltrexone from codeine in this invention, codeine is converted to 6-acetylcodeine, which is N-demethylated to 6-acetylcodeine hydrochloride, followed by alkylating the nitrogen to form 17-cyclopropylmethylnorcodeine. The latter is oxidized to 17-cyclopropylmethylnorcodeinone. For the synthesis of naltrexone from morphine in this invention, morphine is converted to 3-benzylnormorphine as described above in the synthesis of noroxymorphone. 3-Benzylnormorphine is reacted with cyclopropylmethyl halide to produce 3-benzyl-17cyclopropylmethylnormorphine, a novel compound, which is oxidized to 3-benzyl-17-cyclopropylmethyl-normorphinone, a novel compound, by Swern oxidation.

Abstract: The invention provides processes for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. The invention also provides certain novel intermediates.

Abstract: A process is provided for preparing oxycodone from codeine comprising either:(A) the steps of(1) oxidizing codeine so as to form codeinone;(2) converting codeinone to oxycodone in a two-step-one-pot reaction: first reacting codeinone with hydrogen peroxide in water in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone and then catalytically hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone; or(B) the steps of(1) oxydizing codeine so as to form codeinone;(2) reacting codeinone with an acylating agent so as to form codeinone dienol acylate;(3) oxidizing codeinone dienol acylate with an oxidation agent in water or a solubilizing solvent mixture in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone;(4) hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone.

Abstract: A process is provided for preparing 14-hydroxynormorphinones having the formula: ##STR1## which comprises reacting normorphinones having the formula: ##STR2## wherein R is selected from the group consisting of lower alkyl of 1 to 7 carbon atoms, cycloalkyl-lower alkyl with 3-6 ring carbon atoms, benzyl and a substituted-benzyl having the formula: ##STR3## wherein Q and Q.sup.1 are individually selected from the group consisting of hydrogen, lower alkyl, trifluoromethyl, nitro, dialkylamino and cyano;R' is selected from the group consisting of R, 2-(4-morpholinyl)ethyl, benzyloxy carbonyl and R"C(O)-- wherein R" is lower alkyl of 1-4 carbon atoms;with hydrogen peroxide at a temperature of from about 15.degree. C. to about 70.degree. C. in the presence of an acid and an aqueous solvent system to solubilize the reactant for a period of time so as to form the 14-hydroxynormorphinones.

Abstract: Normorphine and normorphinone derivatives are provided as compositions of matter.

Abstract: A process is provided for preparing oxymorphone from morphine by: (a) reacting morphine with an acyl halide or anhydride to form 3-acylmorphine, or (b) reacting morphine with benzyl-halide to form 3-benzylmorphine, and thereafter either by (3a) or (3b):(3a) introducing a .beta.-oriented hydroxy group at the 14-position of the 3-acyl- or 3-benzyl-morphinone with aqueous hydrogen peroxide and an acid at at temperature of about 15.degree. to about 70.degree. C. to form the 3-acyl or 3-benzyl-14-hydroxymorphinone;(3b) acylating the 3-acyl or 3-benzyl-morphinone with an acylating agent so as to form the dienol acylate followed by oxidizing the dienol acetate to the corresponding 3-acyl or 3-benzyl-14-hydroxymorphinone;(4) hydrogenating the 3-acyl-14-hydroxymorphinone with a catalyst so as to form the 3-acyloxymorphone;(5) hydrolyzing the 3-acyl-oxymorphone with aqueous acidic or basic solution to form oxymorphone;(6) hydrogenating the 3-benzyl-14-hydroxymorphinone with a catalyst so as to form oxymorphone.

Abstract: The invention provides processes for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. The invention also provides certain novel intermediates.