Morpholino containing 4-arylpiperidine derivatives

#The present invention relates to novel 4-arylpiperidine derivatives, processes for the production thereof and compositions containing same.

#According to one aspect of the present invention there is provided novel 4-aryl-3/4-amino/hydroxy-piperidine derivatives of the general formula I: ##STR3## wherein R.sub.1 represents hydrogen; lower alkyl; lower aralkyl; lower acyl; aminoalkyl, wherein the alkyl moiety contains 2 to 6 carbon atoms and the amino moiety may be mono- or dialkyl substituted --(CH.sub.2).sub.n --COOH; --(CH.sub.2).sub.n --OH; ##STR4## wherein X is hydrogen or halogen and n is 1, 2, 3 or 4; one of R.sub.2 and R.sub.3 represents a cyano, or a free amino group or a derivative thereof and the other represents a free or protected hydroxyl group; or R.sub.2 represents an azido group when R.sub.3 represents a free or protected hydroxyl group, or R.sub.2 and R.sub.3 together with their associated ring carbons represent an oxazepine ring, and Ar represents an aryl group which may be substituted by lower alkyl, lower alkoxy, halogen or CF.sub.3, as well as addition salts thereof with organic or inorganic acids.

#Since the compounds of formula I have chiral centres at C.sub.3 and C.sub.4, it will be obvious to one skilled in the art that these compounds may be present as stereoisomers and optical isomers. The connotation of the general formulae presented herein is to include all such isomers either separated or in d,l mixtures.

#The present invention will be further described with reference to, but not limited by, the following specific examples.

#A mixture of 2.81 g. of 1-methyl-4-phenyl-3,4-epoxypiperidine and 1.5 g. of piperidine in 10 ml of ethylene glycol was heated at 150.degree. C. in an oil bath overnight (18 hours). The reaction mixture was then cooled, 5 ml. of water added and then extracted three times with an equal volume of methylene chloride on each occasion. The organic fractions so obtained were washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate, filtered and finally evaporated in vacuo to give 3.61 g. of crude 1-methyl-4-phenyl-4-hydroxy-3-(1-piperidyl) piperidine in the form of a resinous residue which was dissolved in ethyl acetate and filtered through a layer of silica gel.

#This compound was then converted to its monohydrochloride by forming a solution in methanol, adding one equivalent of N HCl and evaporating the resulting solution to dryness in vacuo. Further portions of ethanol were added to the residue and the resulting solution in each case was evaporated to dryness. The final residue, which was the desired hydrochloride, when recrystallized from acetone had a melting point of 241.degree.-2.degree. C. The free base was found to be pure by t.l.c. chromatography, by infrared spectroscopy and NMR. The structure of the hydrochloride was confirmed by NMR spectroscopy and elemental analysis. Elemental analysis of the hydrochloride salt was found to be as follows: