Patent GB-1116595-A (GB)
Title: Codeine and morphine derivatives
Inventor: BENTLEY KENNETH WALTER
IPC: C07D489/00
Filed: 1964-07-08
Abstract: Novel derivatives of codeine and morphine having general formulaae <FORM:1116595/C2/1> and <FORM:1116595/C2/2> wherein R represents a hydrogen atom or methyl group, R1 represents an alkyl group of 1 to 3 carbon atoms or an aryl group, R2 represents a hydrogen atom, an alicyclic group with 4 to 6 carbon atoms, an aryl or tetrahydrofurano group, an alkyl or alkenyl group having up to 7 carbon atoms, or an alkyl or alkenyl group containing up to seven carbon atoms substituted on any of carbom atoms 1 to 4 by an alicyclic aryl, alkoxy, aryloxy, morpholino, or tetrahydrofurano group, provided that R2 represents a hydrogen atom only when R1 is aryl, R3 represents a hydrogen atom, an alkyl or alkenyl group with up to 8 carbon atoms, optionally substituted on carbon atoms 1 to 5 by an alkyl, aryl, alicyclic, morpholino or tetrahydroxy furanyl group, R4 represents a single oxygen atom forming part of a carbonyl group, or a hydrogen atom and hydroxy group, and R5 represents an aryl group, and salts thereof with pharmaceutically acceptable acids, are prepared by heating a compound of general formula <FORM:1116595/C2/3> wherein R, R1, R2 and R3 are as defined love with a non-oxidizing mineral acid such as for example with 5-10 N hydrochloric acid, or if R is a hydrogen atom with hydrobromic acid, and if desired reducing the keto group of the re-arranged product with sodium borohydride or with another complex hydride, or by reacting a compound of the first general formula above wherein R3 represents a hydrogen atom with a halide of formula R3Cl, R3Br or R3I, or reacting it with an acyl halide and reducing the resulting amide with lithium aluminium hydride, or by reacting a compound of the second general formula above R, R1 and R2 being as defined above, and R3 being methyl with methyl or ethyl azodicarboxylate to give a compound of general formula <FORM:1116595/C2/4> R, R1 and R2 being as previously defined, and reacting this compound with 5-10 N hydrochloric acid, followed by alkaline treatment to give a compound of the first general formula above where R3 is hydrogen, and if necessary treating with an alkyl halide of formula R3Hal wherein R3 has the above significance, or by reacting acompound of the first general formula above with methyl or ethyl azodicarboxylate to give a compound of formula <FORM:1116595/C2/5> R, R1, R2, and R4 being as previously defined, and reacting this with alkali to give a compound of the first general formula above wherein R3 represents hydrogen and, when required, reacting with an alkyl halide of formula R3Hal, R3 being as previously defined.  Compounds of the first general formula above in which R3 represents a hydrogen atom may be obtained by alkaline hydrolysis of a compound of the first formula above in which R3 is a cyano group.  N - Cyano - 7,8 - dihydro - 31 - (methyl, ethyl, n - propyl, n - butyl and iosbutyl) - 41 - methyl-cyclohex - 31 - eno - (11, 21: 14, 8) norcodeinone are prepared by treating the required N-cyano-6,14 -endetheno - 7 - (2- hydroxy - 2 alkyl)-tetrahydronorthebaine with concentrated hydrochloric acid.