Patent CA-1304369-C (CA)
Title: Azoniaspironortropanol esters and processes for the preparation thereof
Inventor: GRIMMINGER WOLF
IPC: C07D471/20
Filed: 1986-12-29
Granted: 1992-06-30
Abstract: ABSTRACT     The present invention provides a process for the preparation of azoniaspironortropanol esters of the general formula:-                (I) wherein R signifies one of the following radicals: a) an alkylene radical of the general formula:--(CH2)n-CH-(CH2)n-in which R3 is a hydrogen atom or an alkyl, benzyl, aryl or alkoxy radical and n is a whole number of from 1 to 4, b) an alkenylene radical of the general formula:-  in which R4 and R5, which can be the same or different, are hydrogen atoms or alkyl or alkenyl radicals and n is a whole number of from 1 to 4, c) an azaalkylene radical of the general formula:--(CH2)n-N-(CH2)n-in which R6 is a hydrogen atom or an alkyl, alkoxy-carbonyl or acyl radical and n is a whole number of from 2 to 4, d) an oxaalkylene radical of the general formula:--(CH2)n-O-(CH2)n-in which n is a whole number of from 2 to 4, e) an epoxyalkylene radical of the formula:-  f) an o-phenylene radical of the general formula:-  g) a peri-naphthylene radical of the general formula:-  h) a 2,3-quinoxalinene radical of the general formula:-  in which in formulae f) to h), the symbols X and Y, which can be the same or different, are hydrogen atoms or alkyl or alkoxy radicals; and wherein R1 and R2, which can be the same or different, are hydrogen or halogen atoms or alkyl, alkoxy, alkoyl, cyclohexyl, phenyl, alkylphenyl, alkoxyphenyl, halo-phenyl, thienyl or furyl radicals, the alkyl moieties in the said radicals containing up to 6 carbon atoms and being straight-chained or branched, and A ? is the anion of a mono- to tribasic mineral acid, by a) demethylation of tropine to give nortropine, b) reaction of nortropine with a dihalide to give a corresponding azonia compound, and c) esterification of the azonia compound, wherein A) the demethylation of tropine of the formula:                                           (II) is carried out either by working in a C1-C3-chloro-alkane which contains at least one trichloromethyl radical in the presence of an oxidation agent in basic aqueous solution or the tropine is reacted with a chloroformic acid ester in an inert solvent in the presence of an acid-binding agent to give an 8-alkoxy-carbonylnortropine and this is hydrolysed with a base in aqueous solution, B) the nortropine thus obtained of the formula:-             (III) is reacted at ambient temperature for 1 or more days in a dipolar aprotic solvent with a compound of the general formula:-A - R - A     in which A and R have the above-given meanings, in the presence of a secondary or tertiary amine and C) the compound thus obtained of the general formula:-                (IV) in which R and A ? have the above-given meanings, is esterified in an anhydrous, dipolar, aprotic solvent with an imidazolide of the general formula:-                (V) in which R1 and R2 have the above-given meanings, in the presence of a catalyst, and D) when the radical R contains one or more olefinic double bonds in the azonium ring after passing through steps B and/or C, this unsaturated compound is option-ally hydrogenated in a polar solvent with the help of a noble metal catalyst to give the corresponding saturated compound of general formula (I) in which R is a radical a) as defined hereinbefore.