| 摘要 |
<p>1,268,909. Aroyl-piperidines. A. H. ROBINS CO. Inc. 18 June, 1969 [20 June, 1968], No. 30871/69. Heading C2C. Novel compounds of the formula where R denotes acetyl, aryl, carbamoyl, NC 1-8 alkylcarbamoyloxy, carbamoyloxy, aryloxy, aroyl, ethoxy, 4-phenyl-1-piperazinylacetyl, NC 1-8 -alkylcarbamoyl, N,N-di(C 1-8 alkyl)carbamoyl, N-arylthiocarbamoyl, N-arylcarbamoyl, carbethoxy or 2,3-dihydroxypropyl; R<SP>1</SP> denotes H, F, Cl, Br, C 1-8 alkyl, C 1-8 alkoxy or CF 3 ; Y denotes -CH 2 - and n is 0, or 1-4, and acid addition salts thereof, may be obtained by the steps of (1) reacting nipecotic acid or isonipecotic acid with a lower acyl anhydride to form a 1- lower acyl nipecotic or isonipecotic acid, (2) reacting the latter with thionyl halide to form the corresponding acid halide, (3) reacting the product with an aryl compound in the presence of an aluminium trihalide to give a 1-lower acyl- 3- or 4-aroylpiperidine, (4) hydrolysing to form a 3- or 4-aroyl piperidine, (5) reacting the product with an arylalkyl halide, aryloxyalkyl halide, aroylalkyl halide, #-hydroxyalkyl halide, 4- phenyl-1-piperazinyl acetyl chloride, C 1-8 alkyl isocyanate, N,N-di(C 1-8 alkyl) carbamoyl halide, arylisothiocyanate, arylisocyanate, ethyl chloroformate, 2,3-dihydroxypropyl halide, nitrourea, sodium cyanate or 2-bromoethyl ethyl ether; and where an #-hydroxyalkyl halide is used, (6) reacting the 1-(#-hydroxyalkyl)-4-aroylpiperidine with a C 1-8 alkyl isocyanate. 4-Aroylpiperidines may also be obtained by the steps: (1) dehydrating 1-acetyl-4-carbamoylpiperidine to 1-acetyl-4-cyanopiperidine, (2) reacting the product with an arylmagnesium halide to give a 1-acetyl-4-aroylpiperidine, (3) hydrolysing in an acidic medium to give a 4-aroyl-piperidine and reacting the latter as in (5) above. A further preparation of 4-aroyl-piperidines comprises reacting under cyclizing conditions using NaH aγ-[N-(2-haloethyl)-N-substituted]-amino butyrophenone of Formula X Intermediates are prepared by reacting ethanolamine with 2-(p-fluorophenyl)-2-(3-chloropropyl)-1,3-dioxolane to yield 2-(p-fluorophenyl)- 2 - [3 - N - (2 - hydroxyethyl)aminopropyl]- 1,3- dioxolane, reacting this with 2-(o-methoxyphenoxy) ethyl bromide to give p-fluoro-γ[N-2- hydroxyethyl - N - 2 - (o - methoxyphenoxy)- ethyl]-aminobutyrophenone which is acidified with HCl and then reacted with SOCl 2 to form pfluoro -γ- [N - (2 - chloroethyl) - N - (2 - omethoxyphenoxyethyl)amino]butyrophenone hydrochloride. Pharmaceutical compositions useful as tranquillizing agents comprise compounds of Formula I above and a pharmaceutically acceptable carrier, preferably in the form of tablets or soft gelatine capsules.</p> |
