Verfahren zur Herstellung neuer Piperidinderivate

• Main Authors: ZEILE KARL, FRETER KURT, ADICKES FRANZ
• Format: Patent
• Language: German
• Published: 01.12.1966

The invention comprises, as new compounds, compounds of the formula <FORM:0971125/C1/1> and non toxic acid addition salts thereof, wherein R1 is a C1- 4 alkyl group, R2 and R3 are hydrogen or a methyl group, A is a straight or branched alkylene group of 4 to 8 carbon atoms, which may be interrupted by an oxygen or sulphur atom, and X is a fluorine atom or nitro group, also the compound 1-(61-chloro-hexyl)-3b -methyl-4-phenyl-4-carbethoxy -piperidine hydrochloride; a process for the preparation of compounds of the above general formula wherein X may be a nitro group or a halogen atom and R1, R2, R3 and A are as previously defined, by reacting a 4-phenyl-4-carbalkoxy piperidine with a compound X-A-Hal (wherein "Hal" represents Cl, Br or I); a process for the preparation of compounds wherein X is a fluorine atom or a nitro group, by reacting a 3-phenyl-3-carbalkoxy-1, 5-dihalo-pentane, optionally bearing alkyl substituents R2 and R3, with an amine X-A-NH2 (X being fluorine or nitro) and a process for preparing compounds wherein X is an iodine atom or a nitro group by reacting a compound wherein X is chlorine or bromine with an iodide or nitrite, e.g. an alkali-metal iodide or nitrite or silver nitrite. Compounds wherein X is a chlorine or bromine atom may also be made by treating the corresponding 1-hydroxyalkyl-piperidine compound with a halogenating agent such as thionyl chloride or thionyl bromide. The products may be converted into acid addition salts if desired and may be obtained in diastereoisomeric forms by the use of the appropriate diastereoisomeric forms of the starting materials. 3-Methyl-4-phenyl-piperidine-carboxylic esters in diastereoisomeric forms for use as starting materials are made by reacting an N-(b -haloethyl) -N- (b -halopropyl) -N- tosyl-amine with benzyl cyanide, separating the resulting 1-tosyl-3-methyl-4-phenyl-4-cyano-piperidine into the stereoisomeric forms, hydrolyzing and esterifying. Pharmaceutical preparations having analgesic activity comprise the above compounds of the invention (X being a halogen atom or a nitro group), including non-toxic organic and inorganic salts thereof, together with a carrier, preferably in the form of dosage units such as tablets, capsules, suppositories or ampoules of injectable solution.